BRCA1 and BRCA2 germline testing in Cretan isolates reveals novel and strong founder effects.

Germline BRCA1 and BRCA2 loss-of-function variants have been linked to increased breast and ovarian cancer risk, with more than 5,000 distinct pathogenic variants being reported worldwide. Among individuals of Greek descent, the BRCA1/2 variant spectrum is heterogeneous, but characterized by strong founder effects. As patients from certain geographical regions of Greece (like Crete) were underrepresented in previous studies, we hypothesized that isolated Cretans, a southern Greece islanders' population with distinct demographic, cultural and genetic features, could harbor founder BRCA1/2 mutations. A total of 304 breast or/and ovarian cancer patients of Cretan descent, fulfilling NCCN criteria for genetic testing, were tested by NGS or Sanger sequencing, followed by MLPA. Haplotype analysis was subsequently performed to investigate potential founder effects of recurrent alleles. Overall, 16.5% (50/304) of the tested patients carried 22 different pathogenic variants; 48% in BRCA1, 52% in BRCA2. Three variants, namely two in BRCA2 (Δexons 12 and 13 and c.7806-2A>T) and one in BRCA1 (c.5492del), constituting approximately half (48%) of all detected pathogenic variants, were shown to have a founder effect, with all carriers sharing common haplotypes. Remarkably, these variants were confined to Cretans and have not been identified in other regions of Greece. The high prevalence of specific BRCA1/2 pathogenic variants among Cretans, provides the possibility of cost- and time-efficient screening of the Cretan population. Integrating this knowledge in local public health services may have a significant impact on cancer prevention, and may serve as a starting point for the implementation of testing on a population level.

Effect of a 6-week supervised detraining period on bone metabolism markers and their association with ergometrics and components of the hypothalamic-pituitary-gonadal (HPG) axis in professional male soccer players.

The aim of this study was to examine the effect of a supervised 6-week detraining period on bone metabolism markers, and their association with ergometrics, and components of the hypothalamic-pituitary-gonadal (HPG) axis in elite male professional soccer players. Sixty-seven soccer players (mean age ± SD 23.4 ± 5.2 years) that were following a supervised training program participated in this study. Players were tested twice: immediately after the conclusion of the competition period, and following the detraining period, for the determination of bone-turnover rates, ergometrics, and components of the HPG-axis. The detraining period resulted in significant reduction in osteocalcin [OC] (p < 0.001), C-terminal propeptide of collagen type-I [CICP] (p = 0.002), and bone-alkaline-phosphatase [b-ALP] (p < 0.001) values, while C-terminal telopeptide [CTX] was increased (p < 0.001). No significant relationships were apparent between bone biomarkers and body weight, body-fat %, total testosterone, free testosterone, estradiol, follicle-stimulating hormone, and luteinizing hormone in both experimental sessions (p > 0.05). Similarly, despite the deterioration in ergometrics after detraining (all p < 0.001), no significant correlations were evident (p > 0.05) between bone biomarkers and maximal oxygen consumption, squat jump, countermovement jump, and 20 m sprint performance, and also between % change of bone biomarkers and ergometrics, apart from a weak relationship (p = 0.041) between OC and VO2max of questionable value. Our results suggest that the 6-week soccer off-season detraining period in our study negatively affected bone physiology as reflected by the suppression of bone-formation rate and a parallel induction of bone resorption. The cause of this acute alteration of bone-turnover rates is not related to the examined components of the HPG-axis, although parallels is not associated with the changes in ergometrics.

High density of tryptase-positive mast cells in patients with multiple myeloma: correlation with parameters of disease activity.

Multiple myeloma (MM) is a plasma cell neoplasm characterized by bone marrow infiltration from malignant plasma cells. Mast cells play an important role in inflammation and angiogenesis in malignant diseases. The aim of the study was to evaluate the mast cell density in bone marrow of untreated MM patients with markers of disease activity such as serum interleukin-6 (IL-6), B2M, and C-reactive protein (CRP), the grade of bone marrow infiltration, and the levels of produced paraprotein. We studied 86 newly diagnosed MM patients (46 males, 40 females, mean age 59 ± 13.7 years). Thirty of them reached plateau phase after chemotherapy and 20 healthy volunteers. According to the criteria of International Staging System (ISS) staging system, 23 patients had stage I, 30 had stage II, and 33 had stage III. The serum concentrations of CRP, B2M, and IL-6, and the mast cell density (MCD) values were significantly higher in MM patients' group (1.6 ± 1.8, 4.3 ± 2.9, 7.1 ± 5.1, and 9 ± 4.8), in comparison with those found in control group (0.4 ± 0.1, 1.5 ± 0.6, 1.1 ± 0.5, and 1.9 ± 0.7; p < 0.001 in all the cases). Significant differences were found between the grade of infiltration in bone marrow, and the paraprotein values in patients' serum before and after chemotherapy. Furthermore, there was a significant correlation between the MCD values and the prognostic markers CRP (r = 0.452, p < 0.0001), IL-6 (r = 0.475, p < 0.0001), bone marrow infiltration (r = 0.333, p < 0.0002), and serum paraprotein levels(r = 0.221, p < 0.04). High MCD values strengthen the hypothesis that mast cells participate in the pathogenesis of disease progression and may be used as an indicator of the disease activity.

Comprehensive Analysis of CXCR4, JUNB, and PD-L1 Expression in Circulating Tumor Cells (CTCs) from Prostate Cancer Patients.

CXCR4, JUNB and PD-L1 are implicated in cancer progression and metastasis. The current study investigated these biomarkers in CTCs isolated from metastatic prostate cancer (mPCa) patients at the RNA and protein levels. CTCs were isolated from 48 mPCa patients using the Ficoll density gradient and ISET system (17 out of 48). The (CK/PD-L1/CD45) and (CK/CXCR4/JUNB) phenotypes were identified using two triple immunofluorescence stainings followed by VyCAP platform analysis. Molecular analysis was conducted with an EpCAM-dependent method for 25/48 patients. CK-8, CK-18, CK-19, JUNB, CXCR4, PD-L1, and B2M (reference gene) were analyzed with RT-qPCR. The (CK+/PD-L1+/CD45-) and the (CK+/CXCR4+/JUNB+) were the most frequent phenotypes (61.1% and 62.5%, respectively). Furthermore, the (CK+/CXCR4+/JUNB-) phenotype was correlated with poorer progression-free survival [(PFS), HR: 2.5, p = 0.049], while the (CK+/PD-L1+/CD45-) phenotype was linked to decreased overall survival [(OS), HR: 262.7, p = 0.007]. Molecular analysis revealed that 76.0% of the samples were positive for CK-8,18, and 19, while 28.0% were positive for JUNB, 44.0% for CXCR4, and 48.0% for PD-L1. Conclusively, CXCR4, JUNB, and PD-L1 were highly expressed in CTCs from mPCa patients. The CXCR4 protein expression was associated with poorer PFS, while PD-L1 was correlated with decreased OS, providing new biomarkers with potential clinical relevance.

RETRO-TAS, a Retrospective Observational Study of Trifluridine/Tipiracil in Chemorefractory Metastatic Colorectal Cancer.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) is an oral antimetabolite agent comprised of trifluridine, a thymidine-based nucleoside analogue that inhibits cell proliferation following its incorporation into DNA, and tipiracil that helps maintain the blood concentration of trifluridine by inhibiting the enzyme thymidine phosphorylase which inactivates trifluridine. It is approved as a third-line treatment option for patients with metastatic colorectal cancer (mCRC) and is administered at 35 mg/m2 two times daily from day 1 to 5 and from day 8 to 12 every 28 days. The aim of this investigator-initiated retrospective study (RETRO-TAS; NCT04965870) was to document real-world data on the clinical efficacy of FTD/TPI in patients with chemorefractory mCRC. METHODS: The clinical characteristics of patients with mCRC treated with FTD/TPI in 8 Cancer Centres were collected to assess physician's choice in the third or beyond line of treatment as well as the duration of treatment, dose modification, and toxicity. In addition, other important prognostic features related to mCRC such as molecular profile, performance status (PS), and primary site were analyzed. Statistical analysis for progression-free survival (PFS), overall survival (OS), 6-/8-month PFS rate and disease control rate (DCR) along with Cox regression model, Kaplan-Meier curves, and log-rank tests were carried out by using Stata/MP 16.0 for Windows. RESULTS: From October 2018 to October 2021, a total of 200 patients with mCRC and a median age of 67.0 (IQR 58.0, 75.0) years were treated with FTD/TPI. Τhe median follow-up time was 14 months (IQR 7, 23), 158 PDs and 106 deaths were reported at the time of this analysis. Of all the patients, 58% were males and 58% had mCRC at diagnosis. The molecular analysis identified mutations in KRAS (52%), NRAS (5%), HER2 (3.5%), BRAF (3.5%), and MSI (9%). Previous treatments included radical surgery in 51.5% and adjuvant chemotherapy in 39.5% of patients. FTD/TPI was administered in the third- (70.5%), fourth- (17.0%), or fifth-line (12.5%) treatment setting. Serious adverse events related to FTD/TPI included neutropenia (2%), anaemia (1%), thrombocytopenia (0.5%), diarrhoea (0.5%), nausea (0.5%), and fatigue (4%). A reduction of FTD/TPI dose, delay of next cycle initiation, and shorter duration were reported in 25%, 31%, and 14.5% of patients, respectively. Of all the patients 71.5% received FTD/TPI as monotherapy, 24.5% in combination with bevacizumab, and 4.0% with an anti-EGFR agent. The median FTD/TPI treatment duration was 119.5 days and 81% of patients discontinued treatment due to progressive disease. The DCR recorded by investigators' assessment was 45.5%. The median PFS was 4.8 and the median OS was 11.4 months. The 6- and the 8-month PFS rate was 41.4% and 31.5%, respectively. In the multivariate analysis, PS > 1 and presence of liver and lung metastasis were adversely associated with PFS and OS whereas mutational status and tumor sidedness were not. CONCLUSIONS: RETRO-TAS is a real-world observational study that confirms and adds on the findings of the pivotal RECOURSE Phase III study in relation to the efficacy of FTD/TPI in the third-line setting and in all subgroups of patients regardless of mutational status and sidedness.

Evaluation of Febrile Neutropenia in Hospitalized Patients with Neoplasia Undergoing Chemotherapy.

Febrile neutropenia (FN) is a common but serious complication encountered in patients with cancer and is associated with significant morbidity and mortality. In this prospective study, 63 patients with solid tumors under chemotherapy or immunotherapy were admitted to the hospital due to febrile neutropenia, confirmed through clinical or microbiological documentation. The aim of this study was to provide a comprehensive overview of the epidemiological and microbiological characteristics of hospitalized neutropenic patients with solid tumors undergoing treatment. Additionally, we aimed to assess the duration of neutropenia and identify factors influencing patient outcomes. The median age of patients was 71 ± 10.2 years, most of which were males (66.7%), and the primitive tumor location was the lung (38.1%), with most patients (82.5%) being at disease stage IV. The median duration of neutropenia was three days (range 1-10), and, notably, mucositis was significantly associated with neutropenia lasting ≥3 days (p = 0.012). Patients with lung cancer (38.1%) and patients with stage IV disease (82.5%) presented a higher risk of FN, although these differences did not reach statistical significance. The site of infection was identifiable in 55.6% of patients, with positive cultures detected in 34.9% and positive blood cultures (BC) drawn in 17.5% of cases. Gram-positive bacteria were the predominant causative agents in BC (63.6%), with Staphylococci being the most prevalent among them (66.7%). The median duration of hospitalization was nine days (range, 3-43 days), and most patients showed improvement or cure of infection (16.9% and 74.6%, respectively). Among recorded risk factors, the Eastern Cooperative Oncology Group (ECOG) performance status (PS) appears to be statistically significant. Patients with an impaired PS score (2-4) experienced worse outcomes and higher likelihood of mortality (p = 0.004). Regarding the outcome, a longer duration of neutropenia was also statistically significant (p = 0.050). Of the patients, 12.7% ultimately succumbed to their conditions, with 37.5% attributed to infections. FN is a common yet serious complication in solid tumor patients. Adequate knowledge of the predictors of mortality and the microbiological causes are of utmost importance to allow accurate diagnosis and prompt treatment as they significantly influence patient outcomes.

Prognostic Value of KRAS Mutations in Colorectal Cancer Patients.

Colorectal cancer (CRC) remains a major public health issue. The detection of parameters that affect CRC prognosis is of great significance. KRAS mutations, play a crucial role in tumorigenesis with a strong predictive value. KRAS-mutated stage-IV CRC patients gain no benefit of the anti-EGFR therapy. The KRAS G12C mutation subtype is under investigation for treatment regimens. The present study aimed to detect various RAS mutations in a cohort of 578 RAS-mutated CRC patients; 49% of them had de novo metastatic disease; 60% were male; 71.4% had left-sided tumors; and 94.6% had a good performance status. KRAS mutations were detected in 93.2% of patients, with KRAS G12D being the most common subtype (30.1%). KRAS mutations presented shorter progression-free (PFS) and overall survival (OS), compared with NRAS mutations, although not significantly (PFS: 13.8 vs. 18.5 months; p = 0.552; OS: 53.1 vs. 60.9 months; p = 0.249). KRAS G12D mutations presented better OS rates (p = 0.04). KRAS G12C mutation, even though not significantly, presented worse PFS and OS rates. KRAS exon 3 and 4 mutations presented different PFS and OS rates, although these were not significant. Concluding, KRAS G12D and G12C mutations lead to better and worst prognosis, respectively. Further studies are warranted to validate such findings and their possible therapeutic implication.

Cost-effectiveness of trifluridine/tipiracil as a third-line treatment of metastatic gastric cancer, including adenocarcinoma of the gastrohesophageal junction, among patients previously treated in Greece.

OBJECTIVE: To evaluate the cost-effectiveness of trifluridine/tipiracil (FTD/TPI) compared with best supportive care (BSC) for the treatment of patients with metastatic gastric cancer(mGC), including gastroesophageal junction adenocarcinoma(GEJ), who have received at least two prior therapies for metastatic disease and are eligible for third-line treatment, in Greece. METHODS: A partitioned survival model was locally adapted from a public payer perspective over a 10-year time horizon. Clinical, safety and utility data were extracted from literature. Resource consumption data obtained from a panel of local experts using a questionnaire developed for the study was combined with unit costs obtained from official sources. All costs reflect the year 2020 (€). Outcomes of the model were patients' life years (LYs) and quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratio (ICER) per QALY and LY gained. RESULTS: The total cost per patient was estimated to be €6,965 for FTD/TPI and €1,906 for BSC, while FTD/TPI was associated with 0.180 and 0.107 increments in LYs and QALYs, respectively, compared with BSC, resulting in an ICER of €47,144 per QALY gained and €28,112 per LY gained. CONCLUSION: FTD/TPI was estimated to be a cost-effective treatment option for eligible third line mGC patients, including GEJ in Greece.

Cerebral oximetry monitoring in non-intubated patients undergoing endoscopic retrograde cholangiopancreatography under propofol-induced sedation: a prospective observational study.

BACKGROUND: Prolonged propofol-induced deep sedation increases the risk for sedation-related complications. Cerebral oximetry enables prompt assessment of tissue oxygenation by demonstrating the regional hemoglobin oxygen saturation (rSO2) of the cerebral cortex. This study aimed to: evaluate cerebral oxygenation under deep sedation during an endoscopic retrograde cholangiopancreatography (ERCP) procedure; determine the cerebral desaturation event (CDE) rate; and assess the predictive capacity of CDEs for sedation-related complications. METHODS: All consecutive patients who underwent ERCP between September and December 2019 were included prospectively. Propofol monotherapy was used and sedation level was assessed using the bispectral index (BIS). The target level of sedation was deep sedation, defined by BIS values 40-60. Participants were monitored with arterial blood gas analysis and INVOS 5100C cerebral oximeter. RSO2 values were registered prior to sedation (baseline value), every 5 min during the sedation period and at recovery of consciousness. BIS values were recorded simultaneously. CDE was defined as a drop >10% from individual baseline rSO2. RESULTS: Sixty patients were enrolled. Mean baseline rSO2 was 65.1% and BIS values ranged from 18-85. No significant correlation was observed between mean rSO2 measurements and mean BIS values throughout the recordings (P = 0.193). Data from patients aged ≥65 years were analyzed separately and the results were similar. The CDE rate was 2.7%, but no CDE was associated with clinical manifestations. Twelve sedation-related complications occurred without the presence of cerebral desaturation. CONCLUSION: Cerebral oxygenation remained independent of changes in sedation depth and cerebral oximetry monitoring did not detect complications earlier than standard monitors.

A multicenter phase II trial with irinotecan plus oxaliplatin as first-line treatment for inoperable/metastatic cancer of the biliary tract.

PURPOSE: To evaluate the efficacy and tolerability of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11) as first-line treatment of advanced biliary tract cancer. PATIENTS AND METHODS: Patients with histologically confirmed nonresectable biliary adenocarcinoma were treated with oxaliplatin (85 mg/m(2)) and irinotecan (200 mg/m(2)) every 3 weeks. RESULTS: Twenty-eight patients were enrolled between May 2005 and March 2009. The overall objective response rate was 17.9% with an additional 21.4% of patients with stable disease (disease control rate 39.3%). The median overall survival time was 9.2 months (95% CI 5.8-12.5) and the median progression-free survival time 2.7 months (95% CI 2.2-3.2). Grades 3 and 4 neutropenia occurred in 1 (3.6%) and 4 (14.3%) patients, respectively, and febrile neutropenia in 3 (10.7%). Grade 3-4 diarrhea was observed in 2 (7.1%) patients and grade 3 asthenia in 1 (6%). There were no treatment-related deaths. CONCLUSION: The combination of oxaliplatin and irinotecan has a modest antitumor activity with manageable toxicity as first-line treatment in metastatic cancer of the biliary tract and therefore it cannot be recommended as front-line treatment for unresectable biliary tract cancer.

Age-related and training-induced changes in morphological characteristics of young elite male soccer players.

BACKGROUND: In soccer, morphological characteristics of young players are particularly important as they have a significant impact on the performance of many technical-tactical elements. Our aim in this study was to investigate whether soccer specific training on its own or combined with strength training can influence the morphological characteristics, of young soccer players and if so, to establish which age is more appropriate for interventions through individualized training. METHODS: The study sample consisted of 61 young male soccer players, members of two under 17 (U171 and U172) and two under 19 (U191 and U192) teams. U171 (N.=17, consists of ages: 15.1±0.6) and U191 (N.=14, consists of ages 17.3±0.5 years) teams performed only soccer specific training whilst U172 (N.=18, consists of ages 15.0±0.4 years) and U192 (N.=12 consists of ages 17.1±0.7 years) teams had two extra strength trainings per week. Anthropometric measurements were performed at the beginning and at the end of the 10- months session. RESULTS: Lean body mass was increased whilst body fat decreased at the end of the study in all teams (P<0.001). No significant changes were found regarding endomorphic and ectomorphic outcome. Mesomorphic outcome was significantly increased only in U172 team (P<0.001). CONCLUSIONS: Our data supports that earlier interventions (between ages 15-17 years) in the training routine may be more effective in order to achieve anatomical and morphological characteristics most favorable for soccer.

Recurrence-free Survival and Safety of Imatinib in Patients With Gastrointestinal Stromal Tumour (GIST) in Greece.

AIM: The purpose of the Imadje study was to confirm the efficacy and safety of imatinib, following resection of kit-positive gastrointestinal stromal tumour (GIST), in the adjuvant setting in the Greek population. PATIENTS AND METHODS: A total of 34 adult patients already receiving imatinib were enrolled. Recurrence-free (RFS) and overall survival, as well as time to treatment failure and safety were assessed. RESULTS: Overall survival could not be estimated in the present study, as no death occurred. Overall, 91.2% of patients were recurrence-free at 36 months, while the median time to treatment failure was 35 months. No new or unexpected safety findings were observed. Mutation analysis in 14 patients showed that the most frequent mutations were located in KIT exon 11 (64.3%) and exon 9 (28.6%). Univariate analysis showed that only surgical resection with a margin classification of R0 was associated with better RFS. CONCLUSION: Adjuvant treatment with imatinib for 3 years in patients with intermediate to high risk of recurrence was proven to prolong RFS, while being well-tolerated and not exhibiting a negative impact on patient compliance with therapy.

Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial.

To compare the overall survival (OS) of patients with advanced non-small cell lung (NSCLC) treated with either docetaxel plus gemcitabine or single-agent docetaxel. Chemotherapy-naive patients with advanced/metastatic NSCLC were randomly assigned to receive either DG [n=157; gemcitabine 1100mg/m(2) on days 1 and 8], docetaxel 75mg/m(2) on day 8 or D [n=155; docetaxel 100mg/m(2) on day 1] every 3 weeks. A total of 312 patients were evaluable for toxicity and response. A predefined interim intention-to-treat analysis showed significantly longer median OS (p=0.037) in favor of the DG regimen (9.4 months versus 8.3 months for DG and D regimens, respectively), resulting in the premature termination of the study. The DG regimen was also associated with a significantly higher response rate compared to D (26.8% versus 11.6%, p<0.001). TTP were 3.5 and 2.3 months for the DG and D regimen, respectively (p=0.054). Although there were two treatment-related deaths in the DG arm, the toxicity profiles of the two regimens were comparable. The DG regimen was associated with a significantly better quality of life. The efficacy of the docetaxel plus gemcitabine combination is superior to single-agent docetaxel in chemonaive patients with advanced NSCLC.

Front-line bevacizumab in combination with oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study.

PURPOSE: To evaluate the efficacy and the toxicity of front line FOLFOX4 combined with bevacizumab in patients with metastatsic CRC (mCRC). PATIENTS AND METHODS: Chemotherapy-naïve patients with mCRC, received bevacizumab (5 mg/kg every 2 weeks d1), oxaliplatin (85 mg/m2 on d1), leucovorin (200 mg/m2) on days 1 and 2 and 5-Fluorouracil (400 mg/m2 as i.v. bolus and 600 mg/m2 as 22 h i.v. continuous infusion on days 1 and 2) every 2 weeks. RESULTS: Fifty three patients (46 with a PS 0-1) were enrolled. Complete and partial response was achieved in eight (15.1%) and 28 (52.8%) patients, respectively (ORR: 67.9%; 95% C.I.: 53.8%-92%); 11 (20.7%) patients had stable disease and six (11.3%) progressive disease. With a median follow up period of 13.5 months, time to tumor progression was 11 months while the median survival has not yet been reached; the probability of 1-, 2- and 3- year survival was 79.8%, 63.8% and 58.3%, respectively; Two patients relapsed during the follow up period. Eight (15%) patients underwent metastasectomy with R0 resections. Grade 3-4 neutropenia occurred in 15.1% of patients and one (1.9%) of them presented febrile neutropenia. Non-hematologic toxicity included grade 3 diarrhea (7.6%) and grade 2 and 3 neurotoxicity in 16.9 and 15.1% of patients, respectively. One (1.9%) patient presented pulmonary embolism and one (1.9%) cardiac ischaemia. There was one (1.9%) sudden death after the first cycle. CONCLUSION: The combination of FOLFOX4/bevacizumab appears to be highly effective, well tolerated and merits further evaluation in patients with mCRC.

Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III randomized trial.

PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine (DG) and vinorelbine/cisplatin (VC) combinations in chemotherapy-naive non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Patients with advanced NSCLC were randomly assigned to receive either DG (gemcitabine 1,000 mg/m(2) [days 1 and 8] plus docetaxel 100 mg/m(2) [day 8]) or VC (vinorelbine 30 mg/m(2) [days 1 and 8] plus cisplatin 80 mg/m(2) [day 8]) and prophylactic recombinant human granulocyte colony-stimulating factor (150 microg/m(2) subcutaneously [day 9 through 15]) every 3 weeks. Results A total of 413 randomly assigned patients were analyzed for response and toxicity (DG, n = 197; VC, n = 192). Median survival was 9.0 and 9.7 months (P = .965) for DG and VC arms, respectively; the corresponding 1-year survival rates were 34.3% and 40.8%, respectively. Overall response rate was 30% (95% CI, 23.9% to 36.3%) and 39.2% (95% CI, 32.5% to 45.9%; P = .053) for DG and VC, respectively. Toxicity was as follows (DG v VC): grade 2 to 4 anemia, 34% v 55% (P = .0001); grade 3 to 4 neutropenia, 16% v 37% (P = .0001); febrile neutropenia, 6% v 11% (P = .009); and grade 3 to 4 nausea and vomiting, 1% v 15% (P = .003). Nephrotoxicity occurred in 8% and ototoxicity in 2% of VC-treated patients. There were five and six treatment-related deaths in the DG and VC arms, respectively. Quality of life was improved in DG but not in VC patients. CONCLUSION Although the two regimens produced comparable overall survival, the DG regimen had a better toxicity profile. Therefore, DG could be used in the first-line setting of advanced NSCLC, especially for patients who cannot tolerate cisplatin.

A multicenter phase II study of sequential vinorelbine and cisplatin followed by docetaxel and gemcitabine in patients with advanced non-small cell lung cancer.

PURPOSE: To evaluate the activity and toxicity of the sequential administration of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG regimen) combination in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Fifty-nine previously untreated patients with advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1), and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day 1), (DG regimen) every 2 weeks. RESULTS: One (1.7%) complete and 26 (44.1%) partial responses were achieved for an overall response rate of 45.8% (95% CI 33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive disease. The median time to progression was 5.3 months, the median survival time 12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV neutropenia occurring in 25.5% of patients; all other hematologic and non-hematologic toxicities were relatively infrequent. CONCLUSIONS: The sequential administration of VC and DG regimens was well tolerated and active against advanced NSCLC and merits to be further evaluated against a single doublet.

Correlation of Mast Cell Density With Angiogenic Cytokines in Patients With Active Multiple Myeloma.

PURPOSE: The aim of the study is to estimate whether bone marrow mast cell density (MCD) in multiple myeloma (MM) correlates with circulating levels of various angiogenic factors. METHODS: In 70 patients with newly diagnosed active MM, we measured MCD using immunohistochemical stain for tryptase and serum levels of matrix metalloproteinase 9 (MMP-9), angiopoietin 2 (ANGIOP-2), and angiogenin (ANG) with ELISA. FINDINGS: Levels of MCD, ANGIOP-2, and ANG were significantly higher in MM patients compared with the control group. The MMP-9 level was higher in MM patients compared with the control group but without statistical significance. All values were increasing in parallel with clinical stages. Furthermore, MCD correlated positively with MMP-9, ANGIOP-2, and ANG. IMPLICATIONS: MCs participate in the angiogenic processes of MM, with complex implicated mechanisms. This interplay between MCs and the other participants favors angiogenesis and MM growth.

Clinical practice guidelines for the surgical treatment of rectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO).

In rectal cancer management, accurate staging by magnetic resonance imaging, neo-adjuvant treatment with the use of radiotherapy, and total mesorectal excision have resulted in remarkable improvement in the oncological outcomes. However, there is substantial discrepancy in the therapeutic approach and failure to adhere to international guidelines among different Greek-Cypriot hospitals. The present guidelines aim to aid the multidisciplinary management of rectal cancer, considering both the local special characteristics of our healthcare system and the international relevant agreements (ESMO, EURECCA). Following background discussion and online communication sessions for feedback among the members of an executive team, a consensus rectal cancer management was obtained. Statements were subjected to the Delphi methodology voting system on two rounds to achieve further consensus by invited multidisciplinary international experts on colorectal cancer. Statements were considered of high, moderate or low consensus if they were voted by ≥80%, 60-80%, or <60%, respectively; those obtaining a low consensus level after both voting rounds were rejected. One hundred and two statements were developed and voted by 100 experts. The mean rate of abstention per statement was 12.5% (range: 2-45%). In the end of the process, all statements achieved a high consensus. Guidelines and algorithms of diagnosis and treatment were proposed. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized.

Clinical practice guidelines for the surgical management of colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO.

Despite considerable improvement in the management of colon cancer, there is a great deal of variation in the outcomes among European countries, and in particular among different hospital centers in Greece and Cyprus. Discrepancy in the approach strategies and lack of adherence to guidelines for the management of colon cancer may explain the situation. The aim was to elaborate a consensus on the multidisciplinary management of colon cancer, based on European guidelines (ESMO and EURECCA), and also taking into account local special characteristics of our healthcare system. Following discussion and online communication among members of an executive team, a consensus was developed. Statements entered the Delphi voting system on two rounds to achieve consensus by multidisciplinary international experts. Statements with an agreement rate of ≥80% achieved a large consensus, while those with an agreement rate of 60-80% a moderate consensus. Statements achieving an agreement of <60% after both rounds were rejected and not presented. Sixty statements on the management of colon cancer were subjected to the Delphi methodology. Voting experts were 109. The median rate of abstain per statement was 10% (range: 0-41%). In the end of the voting process, all statements achieved a consensus by more than 80% of the experts. A consensus on the management of colon cancer was developed by applying the Delphi methodology. Guidelines are proposed along with algorithms of diagnosis and treatment. The importance of centralization, care by a multidisciplinary team, and adherence to guidelines is emphasized.