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Background: To identify indicators of guideline-concordant care in lung cancer, to implement such indicators with cancer registry data linked to health databases, and to pilot them in a cohort of patients from the cancer registry of the Milan Province. Methods: Thirty-four indicators were selected by revision of main guidelines by cancer epidemiologists, and then evaluated by a multidisciplinary panel of clinicians involved in lung cancer care and working on the pathway of lung cancer diagnosis and treatment in the Lombardy region, Italy. With a modified Delphi method, they assessed for each indicator the content validity as a quality measure of the care pathway, the degree of modifiability from the health professional, and the relevance to the health professional. Feasibility was assessed using the cancer registry and the routine health records of the Lombardy region. Feasible indicators were then calculated in the cohort of lung cancer patients diagnosed in 2007–2012 derived from the cancer registry of the Milan Province. Criterion validity was assessed reviewing clinical records of a random sample of 114 patients (threshold for acceptable discordance ≤20%). Finally, reliability was evaluated at the provider level. Results: Initially, 34 indicators were proposed for evaluation in the first Delphi round. Of the finally 22 selected indicators, 3 were not feasible because the required information was actually not available. The remaining 19 were calculated on the pilot cohort. After assessment of criterion validity (3 eliminated), 16 indicators were retained in the final set and evaluated for reliability. Conclusion: The developed and piloted set of indicators is now available to implement and monitor, over time, quality initiatives for lung cancer care in the studied health system.

Background: To identify indicators of guideline-concordant care in lung cancer, to implement such indicators with cancer registry data linked to health databases, and to pilot them in a cohort of patients from the cancer registry of the Milan Province. Methods: Thirty-four indicators were selected by revision of main guidelines by cancer epidemiologists, and then evaluated by a multidisciplinary panel of clinicians involved in lung cancer care and working on the pathway of lung cancer diagnosis and treatment in the Lombardy region, Italy. With a modified Delphi method, they assessed for each indicator the content validity as a quality measure of the care pathway, the degree of modifiability from the health professional, and the relevance to the health professional. Feasibility was assessed using the cancer registry and the routine health records of the Lombardy region. Feasible indicators were then calculated in the cohort of lung cancer patients diagnosed in 2007–2012 derived from the cancer registry of the Milan Province. Criterion validity was assessed reviewing clinical records of a random sample of 114 patients (threshold for acceptable discordance ≤20%). Finally, reliability was evaluated at the provider level. Results: Initially, 34 indicators were proposed for evaluation in the first Delphi round. Of the finally 22 selected indicators, 3 were not feasible because the required information was actually not available. The remaining 19 were calculated on the pilot cohort. After assessment of criterion validity (3 eliminated), 16 indicators were retained in the final set and evaluated for reliability. Conclusion: The developed and piloted set of indicators is now available to implement and monitor, over time, quality initiatives for lung cancer care in the studied health system.

The majority of NSCLC patients are elderly, with significant co-pathologies and poor PS. Twenty-five patients with advanced NSCLC were enrolled in this study between October 2002 and April 2006. Sixty percent of them were 65 or older and 48% had a poor PS. The disease was seen to be progressive in all patients after at least one line of chemotherapy. The enrolled patients were treated with 250 mg of gefitinib/day orally. The median overall survival was 2 years from the date of first diagnosis and 12 weeks from the date of first gefitinib administration. One patient showed a partial response and three, stable diseases. Gefitinib was well tolerated, without significant toxicity. EGFR selective inhibitors may therefore be important in the treatment of elderly and/or poor PS patients, who cannot undergo chemotherapy.

The aim of this study was to compare planning target volume (PTV) defined on respiratory-gated positron emission tomography (PET)/CT (RG-PET/CT) to PTV based on ungated free-breathing CT and to evaluate if RG-PET/CT can be useful to personalize PTV by tailoring the target volume to the lesion motion in lung cancer patients.

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates.

Objective: concomitant chemoirradiation with cisplatinum and intracavitary brachytherapy (BT) is the standard of care in patients with locally advanced cervix cancer. Treatment planning for BT provides for the use of three dimensional imaging, such as CT scan or MRI. Positron emission Tomography with [18F] FDG currently used in staging and restaging of this malignancy, is an imaging modality that can aid in image- guided radiation treatment planning. The purpose of our feasibility study was to compare two tumour volumes during BT planning, the CT-based and PET/CT-based clinical target volume (CTVs), in order to evaluate the value of functional imaging in BT planning and if it could be related to a CT standard data set. Moreover a correlation with some clinical data after a median follow up of 47 months is reported. Methods: From June 2007 to May 2010, thirteen women with advanced cervical carcinoma were enrolled into the study. All the patients had a pretreatment PET/CT for staging. All BT fractions have been planned by CT scan and, in the first (BT1) and in the fourth fraction (BT4), FDG-PET/CT was also employed. Two volumes (CTVs) were defined: a CTVstandard, based on clinical information and on CT scan; and a CTVPET-influenced, created with the additional information brought by PET scan. Results: We compared the dimension of the two volumes and the intersection of CTVstandard and CTVPET-influenced at BT1 and BT4. A non-parametric sum rank test was used to determine the statistical significance for comparison of the two series of volumes (CTVstandard and CTVPET-influenced at BT1 and BT4). All patients completed the protocol, but out of 26 attempts of double CTVdefinition, only for 21 cases a comparison between CTVstandard and CTVPET-influenced was made. For two patients at the first BT fraction PET was negative. In the 21 valuable cases, considering both fractions together (BT1 and BT4), the difference between CTVstandard (25.8 ± 7.5 ml) and CTVPET-influenced (21.

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates.

The aim of this study was to evaluate the correlation between the changes of SUV(max) and of apparent diffusion coefficient (ADC) before and after neoadjuvant therapy, to enable us predict the therapy response, in patients with locally advanced rectal cancer (LARC). A total of 30 patients with LARC who underwent CRT were recruited for our study. All the patients underwent a whole body 18F-FDG-PET/CT scan and a pelvic MR examination including DW imaging for staging (PET/CT1 and RM1), and after the chemoradiation therapy (PET/CT2, and RM2). Histopathologic analysis of rectal specimen, according to tumor regression grade (Mandard's criteria) was used as the standard reference. MR and PET-CT images were analyzed, and measurements of ADC values and SUV(max) were taken. Diagnostic performance for selection of complete responders (TRG1-2) and overall diagnostic accuracy for each item were calculated. After neoadjuvant therapy, all patients were submitted to surgery. According to Mandard's criteria, 21 tumors showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders; nine tumors were classified as non responders (TRG3, 4, and 5). In all the patients, mean value of SUV(max) in PET/CT1 was higher than those in PET/CT2 (P < 0.001), whereas mean ADC value was lower in RM1 than RM2 (P < 0.001), with a significant percentage decrease of values after the treatment (P < 0.005).The best predictors cut-off values for TRG response were SUV(max) of 4.4 and ADC of 1.28 × 10(3) mm(2)/s with sensitivity, specificity accuracy, negative predictive value, and positive predictive values of 77.3%, 88.9%, 80.7%, 61.5%, and 94.4%, respectively. We conclude from the overall data of this study that the absolute values of SUV(max) and ADC of rectal lesion after CRT were the best parameters to define the response to treatment, by differentiating fibrosis from viable tumor tissue.

PURPOSE: In order to analyze the changes of glucose metabolism by maximum standardized uptake value (SUVmax) of 18F-FDG PET/CT in patients with rectal cancer submitted to neoadjuvant radiochemotherapy (nRCT) and to correlate SUV changes with tumor regression grade (TRG). METHODS AND MATERIAL: Three sequential 18F-FDG PET/CT studies were performed in 31 patients with rectal cancer at the following time point: before starting the treatment (PET/CT1), during the treatment (PET/CT2), and after completion of neoadjuvant treatment (PET/CT3). The SUVmax values of the rectal lesion in the PET/CT1 (SUV1), PET/CT2 (SUV2), and PET/CT3 (SUV3) were obtained; deltaSUV1 [(SUV1 - SUV2)/SUV1] and deltaSUV2 [(SUV1 - SUV3)/SUV1] were also calculated. Metabolic parameters were compared to TRG. RESULTS: Significant differences in pathologic responder and non-responder patients were found only for SUV2 (6.4 ± 2.9 in responder and 10.7 ± 4.8 in non-responder patients, respectively; P = 0.006) and SUV3 (3.6 ± 1.4 in responder and 6.6 ± 2.1 in non-responder patients, respectively; P = 0.0009). The best predictor for TRG response was SUV3 (threshold of 4.4) with sensitivity, specificity, accuracy, negative predictive value, and positive predictive value of 77.3%, 88.9%, 80.7%, 61.5%, and 94.4%, respectively. CONCLUSION: 18F-FDG PET/CT is a reliable and accurate technique to assess the response to nRCT in rectal cancer. In our population, the absolute value of SUVmax after treatment was the best predictor of pathological response.

Although more advanced techniques such as intensity-modulated radiotherapy are rapidly spreading, 3D conformal radiotherapy (3D-CRT) remains the standard of treatment for many diseases. The authors outline essential indications to guarantee the quality of 3D-CRT treatments. Criteria for clinical indications and potential clinical advantages and disadvantages of 3D-CRT technology are presented. After briefly listing human and technological resources requirements, procedures for 3D-CRT and physical aspects peculiar to 3D-CRT are described. Medical physics support activities are also considered, including suggestions concerning quality control protocols. Difficulties in the application of correct quality procedures, particularly related to human and technological resources, procedures for patient positioning, imaging, contouring, treatment planning, in vivo dosimetry, set-up verification, follow-up, dose delivery are then discussed.

BACKGROUND: Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone. PATIENTS AND METHODS: Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1, and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT. RESULTS: A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms. CONCLUSION: Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.

The majority of NSCLC patients are elderly, with significant co-pathologies and poor PS. Twenty-five patients with advanced NSCLC were enrolled in this study between October 2002 and April 2006. Sixty percent of them were 65 or older and 48% had a poor PS. The disease was seen to be progressive in all patients after at least one line of chemotherapy. The enrolled patients were treated with 250 mg of gefitinib/day orally. The median overall survival was 2 years from the date of first diagnosis and 12 weeks from the date of first gefitinib administration. One patient showed a partial response and three, stable diseases. Gefitinib was well tolerated, without significant toxicity. EGFR selective inhibitors may therefore be important in the treatment of elderly and/or poor PS patients, who cannot undergo chemotherapy. © 2008 Pharma Project Group srl.

Lymphocytopenia is one of the main toxicities of radiotherapy and its severity is related to the irradiation dose. The occurrence of lymphocytopenia depends on the body site of radiotherapy; it is most pronounced with pelvic irradiation, whereas the effect of brain irradiation on the lymphocyte count is to be elucidated. This preliminary study was performed to evaluate changes in lymphocyte number occurring during brain irradiation in cancer patients with brain metastases. The study included 50 patients who received brain radiotherapy for single or multiple brain metastases at a total dose of 30 Gy. Overall, no significant changes in mean lymphocyte number occurred during brain radiotherapy. However, when lymphocyte variations were assessed in relation to the clinical response of brain metastases, a significant increase in the mean number of lymphocytes was found in patients who achieved objective regression of brain metastases on brain irradiation. The mean lymphocyte number decreased in nonresponding patients, albeit without a statistically significant difference with respect to the pretreatment values. The results of this study show that the efficacy of radiotherapy in the treatment of brain metastases is associated with a significant increase in mean lymphocyte number. Therefore, evidence of brain irradiation-induced lymphocytosis may predict the efficacy of radiotherapy.

Aim. The induction of sleep would depend on interaction between gabaergic system and the pineal gland through its main hormone melatonin. Until few years ago benzodiazepines were the only drugs effective in the treatment of insomnia. Recently, however, both melatonin and acupressure have appear to be active in sleep disorders. The aim of study was to evaluate the efficacy of HT 7 point acupressure in insomniac. Methods. The study enrolled 25 patients affected by sleep disorders, 14 of whom had a neoplastic disease. They were treated by HT 7 stimulation for al least two consecutive weeks using a medical device named H7 Insomnia Control®. Results. An improvement in the quality of sleep was achieved in 15/25 (60%) patients, with a more evident efficacy in cancer patients (11/14 [79%]). Conclusion. This study confirms previous clinical data showing the efficacy of acupressure in the treatment of sleep disorders, particularly in cancer-related insomnia.

AIM: The recent rediscovery of the natural traditional medical sciences has contributed to improve the treatment of the human diseases and, in particular, it has been shown that the pharmacological approach is not the only possible strategy in the treatment of nausea and vomiting, since bioenergetic approaches, such as acupressure and acupuncture, may also counteract the onset of vomiting due to different causes. Previous preliminary clinical studies had already suggested a possible efficacy of acupressure also in the treatment of chemotherapy-induced vomiting resistant to the classical antiemetic drugs. The aim of this study was to confirm these preliminary data. METHODS: The study was performed in 100 consecutive metastatic solid tumour patients, who underwent chemotherapy for their advanced neoplastic disease, and who had no benefit from the standard antiemetic agents, including corticosteroids, antidopaminergics and 5-HT 3R-antagonists. Acupressure was made by a stimulation of PC6 acupoint. RESULTS: The emetic symptomatology was reduced by acupressure in 68/100 (68%) patients, without significant differences in relation to tumour histotype. The lowest efficacy was observed in patients treated by anthracycline-containing regimens, without, however, statistically significant differences with respect to the other chemotherapeutic combinations. CONCLUSION: This study confirms previous preliminary clinical results, which had already suggested the potential efficacy of acupressure in the treatment of vomiting due to cancer chemotherapy. Therefore, acupressure may be successfully included within the therapeutic strategies of cancer chemotherapy-induced vomiting.

Background: Despite the well-documented importance of the psycho-emotional status in modulating the anticancer immunity, at present no study has been performed to analyse the influence of the psychological condition on the efficacy of IL-2 cancer immunotherapy. Previous clinical studies have already suggested that the evidence of anxiety may negatively affect the therapeutic efficacy of IL-2 immunotherapy of cancer. Moreover, previous psycho-oncological investigations showed that the suppression of sexual pleasure and sexual identity would represent one of the most frequent psychological profiles in cancer patients. On this basis, a study was planned in an attempt to evaluate relations existing between psychological status, analysed using the Rorschach test and efficacy of IL-2 immunotherapy in the treatment of metastatic renal cell cancer patients. Patients and Methods: The study included 30 consecutive metastatic RCC patients. IL-2 was injected s.c. at a dose of 3 million IU twice/day 5 days/week for 4 consecutive weeks, corresponding to one complete immunotherapeutic cycle, followed by a second cycle after a 21-day rest period. Results: A complete response (CR) was achieved in only 1/30 (3%) patients; a partial response (PR) was obtained in 6/30 (20%) patients. The tumor response rate (CR+PR) was 7/30 (23%) patients. The performance of a psychological analysis was accepted by 24/30 (80%) patients. A normal sexual identity was present in 7/24 (29%) patients. The tumor response rate achieved in patients with sexual identity was significantly higher compared to these who had no sexual identity or who refused the psychological investigation (p<0.05 and p<0.01, respectively). In the same way, the increase in mean lymphocyte number obtained in patients with sexual identity was significantly higher compared to that found in the other two groups of patients. Conclusion: This study demonstrated that the psychological status prior to treatment may be associated with the cl

BACKGROUND AND PURPOSE: There is a widespread and increasing tendency to develop hospital performance indicators in the field of accreditation/certification systems and quality benchmarking. A study has been undertaken to develop a set of performance indicators for a typical radiotherapy Centre and to evaluate their ability to provide a continuous quality improvement. MATERIALS AND METHODS: A working group consisting of radiation oncologists, medical physicists and radiation technologists under the coordination of experts in health technology assessment has elaborated a set of general indicators able to monitor performances and the quality level of a typical radiotherapy Centre. The work has been carried out through four steps: a preliminary set of indicators was selected; data on these indicators were collected in a number of Italian radiotherapy Centres and medical physics Services; problems in collection and analysis of data were discussed; a final set of indicators was developed. RESULTS: A final set of 13 indicators is here presented. They concern general structural and/or operational features, health physics activities and accuracy and technical complexity of the treatment. CONCLUSIONS: The indicators tested in a few Italian Centres of radiotherapy and medical physics Services are now ready to be utilized by a larger community.

Epirubicin and vinorelbine are considered active drugs in metastatic breast cancer. The optimal duration of a chemotherapy regimen for metastatic breast cancer patients is still unknown. Nevertheless, epirubicin has a dose-limiting cardiotoxicity. Vinorelbine is also available as oral formulation. In a multicenter phase II study, we analyzed the feasibility and the efficacy of a maximum of six cycles of i.v. epirubicin plus vinorelbine, followed by oral vinorelbine. We enrolled 30 patients with metastatic breast cancer. Each patient received epirubicin (75 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1-8), every 3 weeks, for three cycles or six cycles in case of objective response or stable disease. When a clinical benefit was obtained, patients received oral vinorelbine (60 mg/m2 on days 1-8 every 3 weeks for three cycles). The regimen demonstrated to be active and well tolerated in metastatic breast cancer, and 6-8 months represented the optimal treatment duration. Maintenance therapy with oral vinorelbine was feasible, effective, safe and well accepted by the patients.

AIM: Alopecia still remains one of the most untreatable side-effects induced by cancer chemotherapy. According to the phytotherapeutic tradition, Panicum Miliaceum has been proven to be effective in the prevention of hair loss for different reasons. At present, however, there are no data about its possible efficacy in the treatment of cancer chemotherapy-induce alopecia. The aim of this study was to analyze the efficacy of Panicum Miliaceum in cancer patients treated with the most potent chemotherapeutic drugs in terms of hair loss, consisting of cisplatin (CDDP) and anthracyclines. METHODS: This case-control study included 28 cancer patients concomitantly treated with Panicum Miliaceum and 56 patients receiving the same combinations of chemotherapy alone as a control group. Panicum Miliaceum was given orally at 300 mg (daily dose) 3 times per day, every day until the end of chemotherapy. The grade of hair loss was assessed by World Health Organization (WHO) criteria. RESULTS: The percentage of alopecia of third grade observed in patients concomitantly treated with Panicum Miliaceum in association with CDDP-containing regimens was significantly lower than that found in those who received the chemotherapy only. The percentage was also lower under anthracycline-containing schedules, without, however, statistically significant differences. Panicum Miliaceum therapy was substantially well tolerated in all patients. RESULTS: This preliminary study would suggest that the concomitant treatment with Panicum Miliaceum may be effective in preventing hair loss induced by CDDP-containing chemotherapies, whereas the benefit was lower in patients treated with anthracyclines. Future randomized studies will be necessary to confirm these preliminary

AIM: Corticosteroids, antidopaminergig agents and 5-HT3 antagonists are the most commonly used drugs in the treatment of chemotherapy-induced vomiting. Acupuncture and acupressure have also appeared to exert antiemetic effects. The aim of this study was to evaluate the efficacy of acupressure in the treatment of chemotherapy-induced vomiting resistant to the standard antiemetic therapies. METHODS: The study included 40 consecutive advanced cancer patients with untreatable chemotherapy-induced vomiting. Colorectal cancer, lung cancer and breast cancer were the neoplasm most frequent in our patients. According to tumour histotype, patients received chemotherapeutic regimens containing the main emetic cytotoxic agents, including cisplatin and athracyclines. Acupressure was made by PC6 point stimulation for at least 6 h/day at the onset of chemotherapy. RESULTS: The therapeutic approach was well accepted by the overall patients. An evident improvement in the emetic symptomatology was achieved in 28/40 (70%) patients, without significant differences in relation to neither tumor histotype, nor type of chemotherapeutic agent. CONCLUSIONS: This preliminary study seems to suggest that a bioenergetic approach by acupressure on PC6 point may be effective in the treatment of chemotherapy-induced vomiting resistant to the conventional pharmacological strategies, as previously demonstrated for vomiting occurring during pregnancy

It has been shown that each manipulation of the mammary region, including breast surgery, may stimulate prolactin secretion. However, it has also been observed that in more than 50% of breast cancer patients surgical removal of the tumor is not followed by enhanced prolactin secretion. This might be indicative of an altered psychoneuroendocrine control of the mammary gland, which could lead to the onset of more biologically aggressive breast cancer. In fact, surgery-induced hyperprolactinemia has been proven to be associated with a better prognosis in terms of survival in node-negative breast cancer patients. The present study was performed to investigate the impact of postoperative hyperprolactinemia on the disease-free survival (DFS) of breast cancer patients with axillary node involvement. The study included 100 consecutive node-positive breast cancer patients who were followed for at least 10 years. Surgery-induced hyperprolactinemia occurred in 45/100 (45%) patients without any significant correlation with the main prognostic variables including number of involved nodes and ER status. The two groups of patients received the same adjuvant therapies. After a median follow-up of 151 months, the recurrence rate in patients with surgery-induced hyperprolactinemia was significantly lower than in patients with no postoperative hyperprolactinemia (23/45 vs 43/55, p<0.01). Moreover, DFS was significantly longer in hyperprolactinemic patients than in patients who had no enhanced secretion of prolactin postoperatively. In agreement with the results described previously in node-negative breast cancer, our study demonstrates the favorable prognostic significance of surgery-induced hyperprolactinemia in terms of DFS duration also in breast cancer patients with axillary node involvement, independent of the other well-known prognostic variables, thereby confirming that the psychoneuroendocrine status of cancer patients may influence the prognosis of their disease.

The hormone resistance of prostate cancer has been proved to depend at least in part on enhanced neuroendocrine activity and the resultant increase in blood concentrations of chromogranin A. Other experimental observations have suggested the involvement of prolactin (PRL), which appears to be a potential growth factor for prostate cancer. Abnormally high levels of PRL have been detected in metastatic prostate cancer, but the clinical significance of this finding has still to be clarified. In an attempt to explain the prognostic significance of serum PRL levels in prostate cancer, in this preliminary study we have analyzed the PRL levels in a group of metastatic prostate cancer patients with hormone-dependent or hormone-resistant cancer. The study included 50 patients with metastatic prostate cancer, 15 of whom had hormone-resistant tumors. The serum levels of PRL were measured by the RIA method. Abnormally high concentrations of PRL were found in 11/50 (22%) patients. Moreover, the percent of patients with cancer-related hyperprolactinemia was significantly higher in the hormone-resistant group than in the hormone-dependent group (8/15 vs 3/35, p < 0.01). This study confirms the possible existence of a hyperprolactinemic state in metastatic prostate cancer, as previously reported by other authors. Moreover, it appears to demonstrate that the occurrence of hyperprolactinemia is more frequent in hormone-resistant neoplasms, suggesting the possible involvement of PRL in hormone independence. Further studies concomitantly evaluating PRL and chromogranin A blood concentrations will be necessary to establish whether the hyperprolactinemia precedes and promotes the onset of hormone resistance in prostate cancer, or whether it is simply a consequence of the hormone independence.

Lymphocytopenia is one of the most negative biological prognostic factors in cancer patients. Lymphocytopenia may depend on tumor progression, or on various anticancer therapies. In particular, radiotherapy (RT) may induce direct lymphocyte damage. The present study was carried out to evaluate the influence of pelvic irradiation on lymphocyte number and lymphocyte subpopulations in patients with gynecologic tumors. The study included 40 patients affected by locally limited or advanced uterine tumors, who underwent pelvic irradiation for a total dose of 50.4 Gy. RT induced a significant decline in total lymphocyte number, with values lower than 500/mm3 in 29/40 (73%) patients and with a mean decrease of 71 +/- 4%. In the same way, T lymphocyte, CD4, CD8 and NK cell mean numbers significantly decreased under RT. The decline in NK and CD8 cells was limited to the first 2-3 weeks of irradiation, whereas that involving T lymphocytes and CD4 cells was progressive and persistent until the end of RT. Finally, the decline in total lymphocyte number was significantly greater in patients who had no tumor regression in response to RT. This study confirms that pelvic RT may induce severe lymphocytopenia which could negatively influence the efficacy of RT itself.

The evaluation of the biological status of cancer patients should not be limited only to investigation of immune reactivity, but should also include analysis of the endocrine condition, namely concerning those hormones which have appeared to be tumor growth factors, such as prolactin (PRL) for breast and prostate carcinomas. This statement is justified by the fact that the evidence of abnormally high serum concentrations of PRL has been proven to be associated with poor prognosis in breast and prostate cancer patients. Moreover, since hyperprolactinemia negatively influences the efficacy of anticancer therapies in breast cancer, it could be fundamental to achieve a normalization of PRL levels by long-acting dopaminergic agents, such as cabergoline. On this basis, a study was planned to evaluate the effect of cabergoline on PRL levels in hyperprolactinemic metastatic breast cancer subjects. The study included 20 hyperprolactinemic metastatic breast cancer subjects, who were randomized to receive no therapy or cabergoline at 0.5 mg/week orally for 4 consecutive weeks. Cabergoline therapy induced a normalization in all patients, whereas no spontaneous normalization of PRL levels occured in the control group. These results show that a weekly oral administration of the long-acting dopaminergic agent cabergoline is a well tolerated and effective treatment of metastatic breast cancer-related hyperprolactinemia. The possible prognostic impact of PRL normalization needs to be established by successive studies.

The evidence of lymphocytopenia has been demonstrated to predict a poor prognosis in terms of survival in advanced cancer patients. This finding is not surprising because of the fundamental role of lymphocytes in mediating tumor cell destruction. Despite the importance of lymphocytes in the pathogenesis of cancer, there are only few data about the profile and the function of lymphocytes during the various antitumor therapies, and in particular the relation between lymphocyte pretreatment number and response to chemotherapy remains to be established. The present study was performed to evaluate whether the evidence of lymphocytopenia before the onset of treatment may influence the efficacy of chemotherapy in metastatic cancer patients affected by the most frequent tumor types. The study included 183 patients (lung cancer: 89; colorectal cancer: 63; breast cancer: 31), 95 of whom had been previously treated with chemotherapy. The chemotherapeutic regimens consisted of oxaliplatin plus 5-fluorouracil and folates in untreated colorectal cancer, weekly irinotecan in pretreated colorectal cancer, cisplatin plus gemcitabine or etoposide in untreated lung cancer, weekly vinorelbine in pretreated lung cancer, and taxotere in breast cancer patients who had been previously treated with anthracyclines. Lymphocyte count was considered to be abnormally low for values below 1500/mm3. Lymphocytopenia was found in 79/183 (43%) patients, without any significant differences in relation to tumor histology. A complete response (CR) was achieved in 6/104 patients with a normal lymphocyte count and in none of the 79 lymphocytopenic patients. A partial response (PR) was obtained in 39 patients with a normal lymphocyte count and in only eight patients with a low lymphocyte count prior to therapy. Therefore, irrespective of the type of chemotherapy, the objective tumor response rate (CR + PR) in lymphocytopenic patients was significantly lower than in patients with normal pretreatment lymphoc

In view of its potential action as a growth factor, the evidence of abnormally high blood levels of prolactin (PRL) is associated with a poor prognosis in metastatic breast cancer. Moreover, metastatic breast cancer-related hyperprolactinemia has proven to counteract the efficacy of cancer chemotherapy. The negative influence of high blood levels of PRL on the efficacy of chemotherapy in metastatic breast cancer has been confirmed by previous preliminary studies, showing that the concomitant administration of the anti-prolactinemic dopaminergic agent bromocriptine may enhance the therapeutic effect of chemotherapy. However, the clinical use of bromocriptine is limited by its short duration and gastrointestinal toxicity. Therefore, new anti-prolactinemic drugs, characterized by less toxicity and a longer duration of activity, such as Cabergoline (CBG), could be more appropriated to control PRL secretion in breast cancer. On this basis, a study was planned to evaluate the efficacy and tolerability of a concomitant administration of CBG with weekly low-dose Taxotere (TXT) in pretreated metastatic breast cancer under chemotherapy. The study group comprised 70 metastatic breast cancer patients (females), pretreated with at least one previous chemotherapeutic line containing anthracyclines, who were randomized to be treated with TXT alone or TXT plus CBG. TXT 25 mg/m2 was given i.v. at weekly intervals for at least 9 consecutive cycles. CBG was given orally at 0.5 mg once per week. Abnormally high pre-treatment levels of PRL were seen in 24/70 (34%) patients, 11 of whom were treated with TXT plus CBG, whereas the other 13 received TXT alone. CBG induced a complete normalization of the PRL levels in all patients within the first two weeks of therapy, whereas no normalization of PRL occurred spontaneously in patients treated with chemotherapy alone. The objective tumor regression rate was significantly higher in patients concomitantly treated with CBG than in those who rece

The recent advances in the knowledge of the psychoneuroimmunological pathogenesis of human neoplasms have demonstrated the existence of feed-back mechanisms operating between interleukins and endocrine secretions, which play an important role in the regulation of the immune responses, including the anticancer immunity. In contrast, few studies only have been performed to investigate the possible relation between endocrine activities and hematopoietic growth factors. The present study was performed to analyze the acute endocrine effects of erythropoietin-alpha (EPO) on the main endocrine secretions. The study was carried out in 10 advanced solid tumor patients. EPO was injected subcutaneously at a dose of 10,000 U, and venous blood samples were collected before and 2, 4 and 6 h after EPO administration. No significant changes in mean serum levels of FSH, LH and TSH were seen in response to EPO. Cortisol and DHEAS concentrations increased after EPO injection, whereas those of PRL decreased, but none of these differences was statistically significant. Finally, mean serum levels of both growth hormone (GH) and somatomedin-C (IGF-1) significantly decreased after EPO administration. This preliminary study shows that EPO may inhibit GH secretion from the pituitary gland and IGF-1 production. Since GH would stimulate EPO release, the results of this study may suggest the existence of feedback mechanism operating between GH secretion and EPO production, with inhibitory effect of EPO on GH secretion, and stimulatory action of GH on EPO production. Therefore, this study would describe the first example of hemato-endocrine feedback mechanisms. Moreover, this study, by showing an inhibitory effect of EPO on IGF-1 secretion, would suggest a possible use of EPO in the medical oncology not only for the treatment of cancer related anemia, but also to counteract tumor growth by blocking IGF-1 production, which has been proven to be a growth factor for several tumor histotypes. Obviou