FOLFIRINOX or Gemcitabine Plus Nab-paclitaxel as First Line Treatment in Pancreatic Cancer: A Real-World Comparison.

Background/Aim: Advanced pancreatic cancer has a poor prognosis and a 5-year survival rate <5%; thus, treatment of patients with advanced unresectable or metastatic disease is challenging. Current guidelines recommend either gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FOL) as first-line treatment. Data on both efficacy and toxicity of FOL versus GnP in metastatic cancer are limited. This study aimed to compare the two chemotherapy regimens in terms of efficacy and toxicity in a real-world setting. Patients and Methods: This retrospective propensity score matching study reviewed the medical records of 123 consecutive patients with advanced or metastatic pancreatic cancer who received either GnP or FOL between March 2013 and January 2019 in Guglielmo da Saliceto Hospital, Piacenza. Results: Fifty patients (40.65%) received FOL, administered in an attenuated dose, and seventy-three patients (59.35%) received GnP. After a propensity matching score, 100 patients were retrospectively evaluated. In the final matched cohort, there was no difference in neoadjuvant therapy, radiotherapy, and surgery performed before the first-line therapy between the two groups. Progression-free survival and overall survival were comparable between the two groups and no difference was found in the percentage of toxicity. Conclusion: There was no difference in outcomes between patients who received FOL and those who received GnP. Unexpectedly, no greater FOL-related toxicity was found, probably due to the dose reduction.

Targeting FGFR Pathways in Gastrointestinal Cancers: New Frontiers of Treatment.

In carcinogenesis of the gastrointestinal (GI) tract, the deregulation of fibroblast growth factor receptor (FGFR) signaling plays a critical role. The aberrant activity of this pathway is described in approximately 10% of gastric cancers and its frequency increases in intrahepatic cholangiocarcinomas (iCCAs), with an estimated frequency of 10-16%. Several selective FGFR inhibitors have been developed in the last few years with promising results. For example, targeting the FGFR pathway is now a fundamental part of clinical practice when treating iCCA and many clinical trials are ongoing to test the safety and efficacy of anti-FGFR agents in gastric, colon and pancreatic cancer, with variable results. However, the response rates of anti-FGFR drugs are modest and resistances emerge rapidly, limiting their efficacy and causing disease progression. In this review, we aim to explore the landscape of anti-FGFR inhibitors in relation to GI cancer, with particular focus on selective FGFR inhibitors and drug combinations that may lead to overcoming resistance mechanisms and drug-induced toxicities.

Prognostic Impact of Ras Mutation on Surgical Strategy in Rectal Cancer Patients Undergoing Neoadjuvant Treatment.

BACKGROUND/AIM: Complete clinical response in rectal cancer after neoadjuvant chemo-radiotherapy is challenging. Indeed, indication to surgery vs. "watch and wait" is a debate due the poor predictive value of restaging exams in order to identify a pathological complete response (pCR). Improving the knowledge on mutational pathways such as MAPK/ERK could be helpful in assessing the real impact of disease on prognosis and in choosing the best therapeutic target. This study aimed to evaluate the significance of biomolecular parameters as prognostic factors in patients undergoing radical surgery after chemo-radiotherapy. PATIENTS AND METHODS: A retrospective analysis was performed including 39 patients who had undergone radical surgery after neoadjuvant chemo-radiotherapy for rectal adenocarcinoma stage II-III through additional evaluation of the following biomolecular markers on surgical specimens: exons 2, 3 and 4 of the KRAS and NRAS genes and exon 15 of BRAF by pyrosequencing. Kaplan-Meier survival curves were plotted to evaluate the association of pathologic response and RAS status with progression-free survival (PFS) and overall survival (OS). The log-rank test was used to assess statistical differences among the survival curves. RESULTS: Data analysis showed RAS mutation in 15 patients (38.46%). pCR was achieved in seven patients (18%), including only two RAS mutation cases. The distribution of evaluated variables was homogeneous in the two groups based on pathological response. The Kaplan-Meier curve showed poor outcomes in OS and PFS in patients with RAS mutation (p=0.0022 and p=0.000392, respectively), but no significant differences based on pathological response for both OS and PFS. CONCLUSION: RAS mutation seems to be related to poor prognosis and increased risk of recurrence in rectal cancer patients undergoing radical surgery after chemo-radiotherapy.

Randomized trial of sucrosomial iron supplementation in patients with chemotherapy-related anemia treated with ESA.

BACKGROUND: Iron supplementation improves the erythropoiesis-stimulating agents' (ESAs) response in chemotherapy-related anemia. The primary aim of our study is to assess the efficacy of sucrosomial iron, a new oral iron formulation, in cancer patients with chemotherapy-induced anemia treated with ESAs. The secondary objectives included the efficacy into two subgroups of patients (iron replete and functional iron deficiency) between the two study arms, safety and the effect on transfusion need. METHODS: In this randomized, multicentre, open-label, phase III clinical trial, 60 cancer patients were enrolled. Each patient was randomly assigned (1:1) to receive 12 weeks of oral sucrosomial iron at the dose of 30 mg daily in combination with ESAs or no supplementation to ESA treatment. The endpoint considered for efficacy was the proportion of patients achieving complete hematological response at 12 weeks (increase in Hb > 2 g/dL from baseline, without RBC transfusions in the previous 28 days or achieving Hb ≥ 12 g/dL). RESULTS: There was a statistically significant association between oral sucrosomial iron supplementation in combination with ESAs and the achievement of a complete hematological response. This response was achieved within 12 weeks by 31% of patients in the control group and by 52% of patients supplemented with oral sucrosomial iron. A trend of greater response in sucrosomial iron arm was found in both subgroups. No difference was observed about safety and transfusion need. CONCLUSIONS: Sucrosomial iron is well tolerated and its combination with ESAs improves the hematological response in cancer patients with chemotherapy-related anemia. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: This study has been reviewed by the Institutional Ethics Committee of the IRCCS Policlinico San Matteo Foundation, Pavia, Italy (28/04/2015; prot. N. 20,150,002,059), and by the Institutional Ethics Committee of the other Italian oncological centers involved in this study.

Central venous catheterization in cancer patients with severe thrombocytopenia: Ultrasound-guide improves safety avoiding prophylactic platelet transfusion.

Prior research has revealed that ultrasound (US) guided central venous catheterization (CVC) is associated with a reduction in the complication rate such as pneumothorax and an improved first-pass success placing CVC in the internal jugular vein. The present study investigated if US-guided CVC, in a subset of cancer patients with severe thrombocytopenia, reduced bleeding risk and avoided prophylactic platelet transfusion. The efficacy and safety of US-guided CVC placement in cancer patients with severe thrombocytopenia was retrospectively analyzed over a period of 9 years (Dec 2000-Jan 2009), 1,660 and 207 patients with cancer underwent US-guided CVC placement into internal jugular vein respectively at the Department of Onco-Haematology, Hospital of Piacenza. The first group of patients included patients in active antitumor treatment, while the second group included patients in the palliative phase. A total of 110 (5.89%) of these 1,867 patients exhibited severe thrombocytopenia defined as platelet count ≤20x109/l, and formed the basis of this study. All procedures were evaluated for bleeding complications as defined by the National Institute of Health Common Terminology Criteria for Adverse Events (CTCAE 3.0). In the subgroup of the 110 patients with severe thrombocytopenia a single needle puncture of the vein was employed in 121 of the 122 procedures (99.18%) and no attempt failures were registered. No pneumothorax, no major bleeding and no nerve and arterial puncture were reported, only one self-limiting hematoma (0.90%) at the site of CVC insertion was reported (CTCAE 3.0 grade 1). No platelet transfusions were performed in the 110 patients, pre and post CVC placement. We believe that US-guided CVC insertion procedures into the internal jugular vein makes the difference in safety, also in thrombocytopenic patients avoiding prophylactic or post procedure platelet transfusion.

Feasibility and Utility of Incorporating Patient-Reported Outcomes into Surveillance Strategies for Advanced Lung Cancer.

PURPOSE: To identify and to describe patient-reported outcomes (PROs) in lung cancer patients and to evaluate the feasibility and utility of PROs into surveillance strategies, a review was carried out. PATIENTS AND METHODS: A systematic search in bibliographic databases evaluating the instruments used in PROs of non-small-Cell lung cancer (NSCLC) patients was done. RESULTS: From August 2014 to August 2019, 33 studies were included in this review and 16,491 patients were evaluated. PROs were divided into 6 different categories: 1) PROs as a guide in therapeutic choice, 2) PROs as indicator of disease progression, 3) agreement between PROs and the evaluated parameters, 4) PROs to evaluate the effects of immunotherapy, 5) need to deepen the knowledge of PROs, and 6) use of new electronic PROs. CONCLUSION: The most frequently used instruments are EORTC QLQ-30 (16, 50%) and EORTC LC-13 (14, 43.75%) and in some studies (37.5%) they are used together. For different reasons (disease progression, adverse event, death, incomplete participation, etc.), the completion of these instruments decreased over time from baseline to subsequent measurements. This review demonstrates that PROs can play an important role as part of health care, and that routine use implementation could improve patient management in addition to the traditionally collected outcome.

Modified FOLFIRINOX for unresectable locally advanced/metastatic pancreatic cancer. A real-world comparison of an attenuated with a full dose in a single center experience.

Purpose: Metastatic pancreatic adenocarcinoma has a very poor prognosis. Although irinotecan, oxaliplatin and leucovorin-modulated fluorouracil (FOLFIRINOX) significantly increases survival in advanced pancreatic cancer, compared to employing only gemcitabine (GEM), toxicities have tempered enthusiasm for its use. Methods: This study retrospectively analyses the real-world clinical practice with full and attenuated doses of FOLFIRINOX in unselected patients with locally advanced unresectable or metastatic pancreatic cancer, treated at an Italian general hospital. Efficacy, tolerability, and toxicity were evaluated, and overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method. Results: Fifty consecutive patients with advanced (13) or metastatic (37) pancreatic adenocarcinomas were treated with FOLFIRINOX at the Medical Oncology Unit, Piacenza General Hospital, North Italy. The first enrolled consecutive 18 patients (36%) of this series started the treatment with a full dose of the regimen, while the subsequent 32 (64%) consecutive patients received dose attenuation (-20% bolus fluorouracil and -25% irinotecan). In the entire group, the response rate, median OS, and median PFS were 30%, 10.1 months, and 5.6 months, respectively, with no differences in objective response in the 32 patients that received an attenuated dose compared with the 18 patients receiving a full dose of chemotherapy. However, neutropenia, anemia, fatigue, and vomiting were statistically increased in the 18 patients receiving a full dose compared with the 32 patients receiving an attenuated dose of FOLFIRINOX (p<0.05). Conclusion: This study demonstrates the efficacy and tolerability of modified FOLFIRINOX in advanced and metastatic pancreatic cancer.

Immune checkpoint inhibitors in EGFR-mutation positive TKI-treated patients with advanced non-small-cell lung cancer network meta-analysis.

Non-Small Cell Lung Cancer (NSCLC) patients with Epidermal Growth Factor Receptor (EGFR) mutation benefit from a first line of treatment with tyrosine kinase inhibitors (TKIs). After progression, the choice of treatment is between chemotherapy and immune checkpoint inhibitors, but the role of EGFR mutation in the response to immunotherapy is still unclear. A network meta-analysis was performed and 4 randomized trials comparing immune checkpoint inhibitors versus chemotherapy were identified. A Bayesian network meta-analysis was carried out to compare three checkpoint inhibitors (nivolumab, pembrolizumab and atezolizumab) versus chemotherapy (docetaxel), evaluating their Hazard Ratio (HR) and 95% Confidence Interval (CI) for Overall Survival (OS). Results suggest that patients with NSCLC and EGFR mutation, previously treated with TKIs, show better OS when treated with docetaxel in comparison to checkpoint inhibitors treatment.

Systematic vs. on-demand early palliative care in gastric cancer patients: a randomized clinical trial assessing patient and healthcare service outcomes.

PURPOSE: Early palliative care (EPC) has shown a positive impact on quality of life (QoL), quality of care, and healthcare costs. We evaluated such effects in patients with advanced gastric cancer. METHODS: In this prospective, multicenter study, 186 advanced gastric cancer patients were randomized 1:1 to receive standard cancer care (SCC) plus on-demand EPC (standard arm) or SCC plus systematic EPC (interventional arm). Primary outcome was a change in QoL between randomization (T0) and T1 (12 weeks after T0) in the Trial Outcome Index (TOI) scores evaluated through the Functional Assessment of Cancer Therapy-Gastric questionnaire. Secondary outcomes were patient mood, overall survival, and family satisfaction with healthcare and care aggressiveness. RESULTS: The mean change in TOI scores from T0 to T1 was - 1.30 (standard deviation (SD) 20.01) for standard arm patients and 1.65 (SD 22.38) for the interventional group, with a difference of 2.95 (95% CI - 4.43 to 10.32) (p = 0.430). The change in mean Gastric Cancer Subscale values for the standard arm was 0.91 (SD 14.14) and 3.19 (SD 15.25) for the interventional group, with a difference of 2.29 (95% CI - 2.80 to 7.38) (p = 0.375). Forty-three percent of patients in the standard arm received EPC. CONCLUSIONS: Our results indicated a slight, albeit not significant, benefit from EPC. Findings on EPC studies may be underestimated in the event of suboptimally managed issues: type of intervention, shared decision-making process between oncologists and PC physicians, risk of standard arm contamination, study duration, timeliness of assessment of primary outcomes, timeliness of cohort inception, and recruitment of patients with a significant symptom burden. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01996540).

Prognostic role of aspartate aminotransferase-lymphocyte ratio index in patients with metastatic colorectal cancer: results from the randomized ITACa trial.

BACKGROUND: The aim of this study was to investigate the role of pre-treatment aspartate aminotransferase-lynphocyte ratio (ALRI) as a predictor of prognosis and treatment efficacy in patients with metastatic colorectal cancer (mCRC) enrolled in the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) + bevacizumab (B) or CT alone. PATIENTS AND METHODS: Patients randomly received CT+B or CT alone as first-line therapy. CT consisted of either FOLFOX4 or FOLFIRI at the clinician's discretion. RESULTS: Out of the 284 patients enrolled, increased ALRI levels were associated with shorter PFS and OS (p<0.0001). At baseline, median PFS was 10.3 months (95% CI 9.4-12.0) and 8.0 months (95 % CI 6.8-8.9), and median OS was 25.2 months (95 % CI 21.3-30.2) and 18.8 months (95 % CI 16.6-21.7) for patients with low (<14) and high (≥14) ALRI levels, respectively (HR 1.43, 95% CI 1.12-1.82, p=0.004; HR=1.51, 95% CI 1.17-1.96, p<0.001). Interaction tests on ALRI levels and treatment efficacy in the CT+B and the CT groups were statistically significant for PFS (p=0.0003), but not for OS (p=0.228). CONCLUSION: Our results indicate that ALRI is a good prognostic and predictive marker for mCRC patients candidate for CT+B.

Second-line chemotherapy for the treatment of metastatic pancreatic cancer after first-line gemcitabine-based chemotherapy: a network meta-analysis.

Guidelines for treatment of metastatic pancreatic cancer recommend a second line based on Fluoropyrimidine (FP) alone or in combination with Oxaliplatin (OXA) or Irinotecan (IRI) after a first line treatment based on Gemcitabine (GEM). We conducted a Bayesian network meta-analysis to compare currently available therapies to treat metastatic pancreatic cancer in the second line, considering as efficacy measures overall survival (OS) and progression free survival (PFS). Published randomized trials were identified using electronic databases (MEDLINE, PubMed, https://clinicaltrials.gov/ and American Society of clinical oncology). 8 studies met the inclusion criteria for a total of 1,587 patients and 7 different therapeutic schemes. The results suggested that the use of IRI-FP-Folinic Acid scheme in the second-line treatment of metastatic pancreatic cancer may offer a benefit in terms of OS and PFS for patients not previously treated with these drugs.

Can early palliative care with anticancer treatment improve overall survival and patient-related outcomes in advanced lung cancer patients? A review of the literature.

PURPOSE: Metastatic non-small-cell lung cancer (NSCLC), the leading cause of death from cancer worldwide, is a debilitating disease that results in a high burden of symptoms and poor quality of life; the estimated prognosis after the diagnosis has been established was less than 1 year until some years ago. At the present, the new targeted therapies and immunotherapy are changing the course of the disease. However, advanced NSCLC remains an incurable disease, with a poor prognosis for the majority of the affected patients, so that quality of life and relief from symptoms are primary objectives of treatment. Some evidences suggest that early palliative care (EPC) for these patients can improve quality of life and even survival. DESIGN: A systematic review of the studies evaluating the impact on objective and on patient-reported outcomes of the introduction of EPC in opposition to standard care (SC), for advanced lung cancer patients, was performed. Because of the small number of studies conducted in this area, retrospective studies were also considered for the review. RESULTS: Five studies were included because they matched the inclusion criteria previously defined as relevant for the study. The review found that both survival and quality of life were better for patients included in EPC groups. CONCLUSIONS: While results of the studies included in this review are not always comparable because different methods and scales have been used, there is enough evidence for clinical oncologists to implement the use of EPC in clinical practice for advanced lung cancer patients.

Gastric cancer with brain metastasis and the role of human epidermal growth factor 2 status.

Central nervous system (CNS) metastases from cancers of the gastrointestinal tract (GIT) are rare, and occur in 0.16-0.69% of patients with gastric or gastro-esophageal (GE) junction cancer. Overexpression of the human epidermal growth factor 2 (HER-2) is associated with poor prognosis in the absence of HER-2-targeted therapy, and with an increased incidence of CNS metastases in patients with breast cancer. The role of HER-2 overexpression in CNS metastases is not well known in gastric adenocarcinoma. The purpose of the present retrospective study was to assess the incidence of CNS metastases and to evaluate the associations between the CNS and HER-2 status in a series of consecutive patients with gastric or GE junction cancer. Between 2007 and 2013, 300 patients with gastric cancer (GC) or gastroesophageal junction, were admitted to Piacenza General Hospital, Italy. These cases were retrospectively analyzed to evaluate CNS metastases. The metastases were diagnosed with imaging techniques performed on symptomatic patients. Gastric histological samples of patients with CNS metastases were reviewed and tested for HER-2. A total of 7 of the 300 patients (2.33%) with GC were observed to have CNS metastases and 6 (85.71%) had HER-2 positive disease. These patients exhibited a poor prognosis with a median overall survival rate of 4.1 months (range, 2.1-6.6 months). These results suggested there may be CNS recurrence susceptibility in patients with HER-2 positive GC. To the best of our knowledge, this is the first report that associates CNS metastases and HER-2 status in gastric or GE junction cancer.

Prevalence study on potential drug-drug interaction in cancer patients in Piacenza hospital's Onco-Haematology department.

Background Cancer patients can be a human model of potential drug interactions. Usually they receive a large number of different medications, including antineoplastic agents, drugs for comorbid illness and medication for supportive care, however information about these interactions are fragmented and poor. Objective We assessed a prospective study to evaluate the prevalence of drug interaction among patients hospitalized in the Onco-Haematology department, Hospital of Piacenza. Methods Data on drugs administered for cancer, comorbidities, or supportive care were collected from different computerized prescription software in use in the department; we compared them with a database to focus on the co-administration of drugs. A literature review was performed to identify major potential drug interaction and to classify them by level of severity and by strengths of scientific evidence. Results In this study 284 cancer patients were enrolled; patients had taken an average of seven drugs on each day of therapy plus chemotherapeutic agents, we identified 67 potential drug interactions. At least 53 patients had one potential drug interaction. Of all potential drug interactions 63 were classified as moderate severity and only four as major. In 55 cases chemotherapeutic agents were involved in possible interactions with supportive care drugs, meanwhile in 12 cases the potential drug interactions were between supportive care drugs. Conclusions In our centre, thanks to a computerized prescription software, integrated with caution alarm in case of possible interaction, we had a lower rate of potential drug interactions than the one from literature. It is possible to improve the software integrating the alarm with the potential drug interactions between chemotherapy agents and supportive care drugs.

Thoracentesis in advanced cancer patients with severe thrombocytopenia: Ultrasound guide improves safety and reduces bleeding risk.

BACKGROUND: Patients with severe thrombocytopenia are considered at risk for bleeding during invasive procedures as thoracentesis. The use of ultrasound (US) significantly reduces the rate of pneumothorax from thoracentesis, but there is a lack of data on safety and efficacy of US guidance in reducing bleeding complications in thoracentesis performed on patients with severe thrombocytopenia. METHODS: We retrospectively analysed the efficacy and safety of thoracentesis in cancer patients with severe thrombocytopenia. From January 2005 to December 2011, 462 patients underwent thoracentesis. Procedures were divided into 2 groups: performed without or with US guidance. All procedures were evaluated for bleeding complications as defined by the National Institutes of Health Common Terminology Criteria for Adverse Events. RESULTS: A total of 436 consecutive evaluable thoracentesis were analysed. Thoracentesis was performed with US guidance in 310 cases. Forty-one patients (9.40%) had severe thrombocytopenia. In 32 of these 41 patients, thoracentesis was performed under US guidance while in 9 cases the procedure was performed without US guidance. Three mild haemorrhagic complications (0.69% of the procedures performed) were observed and all occurred in group of the 9 (33.33%) patients with severe thrombocytopenia who underwent thoracentesis without US guidance. No haemorrhagic complications were recorded in the 427 patients, including the 32 patients with severe thrombocytopenia, in whom thoracentesis was performed with US guidance. CONCLUSIONS: US guided thoracentesis is a safe and effective approach in cancer patients with severe thrombocytopenia. Our results indicate that this procedure, when US-guided, can be safety performed even in patients with platelet count below 30 × 109 /L.

Prognostic value of MGMT promoter status in non-resectable glioblastoma after adjuvant therapy.

BACKGROUND: Methylation of MGMT promoter has been identified as a favourable predictive factor of benefit from XRT/TMZ → TMZ. Patients with non-resectable glioblastoma (GBM) generally exhibit a poor prognosis, even after XRT/TMZ. Few data are available concerning the predictive value of MGMT promoter methylation in this population. METHODS: This is an observational retrospective study in patients with malignant brain glioma, treated between June 2008 and October 2011 and followed up until April 2012 at the Neurosurgery-Neurotraumatology Unit of the University Hospital of Parma and at the Neurosurgery Unit of IRCCS "ASMN" of Reggio Emilia, Italy. The medical records of an overall number of 174 patients with a newly diagnosed GBM were reviewed. Volumetry analysis of the lesions was performed on pre- and post-operative neuroimaging by Voxar 3D Ebit AET software. The genetic characterization was performed on paraffin embedded tissue from all resected tumours. Isolation of nucleic acids, bisulfite modification of DNA, methylation-specific PCR and sequencing analyses were done mainly on fresh tissue from biopsy withdrawals. Within 3-4 weeks after either biopsy or surgery, patients were assigned to receive XRT/TMZ→TMZ: treatment included XRT (60 Gy in 30 fractions)/TMZ (daily dose of 75 mg/m(2))/TMZ (150-200mg/m(2) per day for 5 days of every 28-day cycle). RESULTS AND DISCUSSION: A total of 55 consecutive patients (23 men, 22 women) fulfilled inclusion criteria consisting of age over 18 years, supratentorial histologically proven primary malignant glioma, complete determination of the MGMT methylation status, no prior history of surgery, XRT and/or chemotherapy, adequate clinical and radiological follow-up no lesser than 6 months. Twenty-three patients underwent neuronavigation needle biopsy (B Group) and thirty-two patients were operated with craniotomy for tumour resection (R Group). The pre-operative mean age was similar between groups (61.7 ± 10.7 vs 60.3 ± 11.8 years in the B and R groups respectively; p>0.05). The B groups showed a slightly lower KPS than the R Group (82.1 ± 17.3 vs 90.3 ± 14.1 respectively; p>0.05). The mean pre-operative volume of the tumour did not differ between groups (46.2 ± 40.2 cm(3) vs 44.1 ± 33.2 cm(3) in the R Group and B Group respectively; p>0.05). The MGMT promoter was methylated in 12 patients (51.2%) of B Group and in 17 patients (53.1%) of R Group. XRT/TMZ → TMZ was accomplished in 11 patients (47.8%) of B Group and in 24 patients (75%) of R Group; in 24/29 methylated patients (82.8%) and in 11/26 unmethylated patients (42.3%). Survival analysis of methylated vs unmethylated tumours was statistically significant (Log Rank Mantel Cox: 0.019 in B Group and 0.023 in R Group). In B Group the mean overall survival (OS) of methylated patients was 11.4 months (IC 95% 6.5-16.4) vs 4.8 months (95% IC, 2.6-7.0) of unmethylated patients. In R Group the mean OS was 21.7 months (95% IC, 16.9-26.6) for methylated patients and 14.0 months (95% IC, 8.5-19.4) for unmethylated patients. At the multivariate Cox regression analysis conducted on the total population (55 patients), XRT and TMZ were found to be predictive of OS. In the R Group, KPS, XRT and TMZ correlated with a better outcome. In the B Group, XRT and MGMT promoter methylation were favourably related with OS. CONCLUSION: MGMT promoter unmethylation has a predominant unfavourable impact on clinical outcomes even in the subpopulation of patients with non-resectable GBM. The unmethylated MGMT promoter status could be considered the main predictor of poor prognosis in biopsied GBM, due to the greater probability of patients not having benefits from adjuvant therapies and not being able to accomplish XRT/TMZ → TMZ. The frameless neuronavigation biopsy technique is safe and effective for predictive evaluation and could help in treatment decision making.

Malignant pleural mesothelioma metastatic to the submandibular salivary gland, simulating glandular hypertrophy, diagnosed by fine-needle aspiration biopsy: a case report and literature review.

BACKGROUND: Malignant mesothelioma is a rare neoplasm that generally develops in the pleural or peritoneal cavity. Distant metastases are common; it rarely metastatizes to the head and neck region. CASE PRESENTATION: A 54-year-old white man, a non-smoker, was treated with chemotherapy, surgery and radiation for a malignant pleural mesothelioma. Seven months after the last treatment, he developed a right submandibular enlargement: clinical examination, ultrasound and computerized tomography scans revealed a salivary gland hypertrophy. Anti-inflammatory and antibiotic treatment was then started, without improvement. An ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) showed atypical mesothelial cells with nuclear enlargement and increased chromatin representation. Immunocytochemistry showed positivity for calretinin and WT-1.A diagnosis of right submandibular salivary gland involvement from mesothelioma was established, allowing an adequate treatment. CONCLUSION: We report a very rare site of metastasis from malignant pleural mesothelioma. We suggest that US-guided FNAB is a useful, quick, and cheap procedure for a definite diagnosis.

Intrapleural Trastuzumab Therapy for Malignant Pleural Effusion from HER2 Overexpression in Metastatic Gastric Cancer.

BACKGROUND: Malignant pleural effusion (MPE) is an extremely common problem affecting cancer patients with advanced disease. The current therapy for MPE is local treatment, such as thoracentesis, chemical pleurodesis, intracavitary administration of anticancer drugs and systemic therapy. However, the management of MPE is still unsatisfactory. CASE: We report a case of MPE secondary to human epidermal growth factor receptor 2 (HER2)-positive gastric cancer that was successfully treated with intrapleural trastuzumab. A 52-year-old male with metastatic HER2-positive gastric cancer received chemotherapy (FOLFOX4 regimen) plus trastuzumab; after 11 courses of chemotherapy, he developed right MPE refractory to systemic treatment and pleurodesis. A pleural biopsy performed during thoracoscopy showed pleural metastasis from HER2-positive gastric cancer. The patient received 2 courses of intrapleuric trastuzumab. After the second course, the MPE disappeared, and he continued systemic therapy with trastuzumab and docetaxel. CONCLUSION: The safety was good, no local or systemic complications occurred, and the dyspnea secondary to MPE improved and subsequently disappeared. To our knowledge, this case is the first report on intrapleuric trastuzumab use to treat refractory MPE secondary to metastasis from HER2-positive gastric cancer. The treatment was well-tolerated and efficacious.