Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro.

STUDY QUESTION: Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? SUMMARY ANSWER: The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. WHAT IS KNOWN ALREADY: Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. STUDY DESIGN, SETTINGS, SIZE AND DURATION: This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. MAIN RESULTS AND THE ROLE OF CHANCE: The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. LIMITATIONS, REASONS FOR CAUTION: Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo. WIDER IMPLICATIONS OF THE FINDINGS: GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage.

Is perineural invasion (PN) a determinant of disease free survival in early stage colorectal cancer?

BACKGROUND/AIMS: The prognostic importance of perineural invasion (PN) in colorectal cancer (CRC) is unclear. The aim of this study to find out whether the PN was an independent stratification factor of postoperative relapse in curatively resected high-risk stage II & III CRC patients who were treated with adjuvant therapy. METHODOLOGY: Data of patients with high risk stage II & all stage III CRCs treated with adjuvant chemotherapy were retrospectively analyzed. Pathological features of final surgical specimen were noted. Disease-free survival was determined by Kaplan-Meier estimator, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test. RESULTS: PN was found to be positive in 26% in the files of 593 eligible patients. In 21% of the reports PN status was not reported. Presence of PN in the resected primary tumors did not have independent effect on DFS. Further analyses for importance of PN on DFS of colon or rectal cancers did not show any effect. CONCLUSIONS: This study had failed to demonstrate any prognostic effect of PN for DFS in surgically resected stage II and III CRC patients who received adjuvant treatments.

Analysis of PTEN, BRAF and PI3K status for determination of benefit from cetuximab therapy in metastatic colorectal cancer patients refractory to chemotherapy with wild-type KRAS.

We investigated predictive values of BRAF, PI3K and PTEN in cetuximab responses in KRAS wild-type (+) chemotherapy refractory, metastatic colorectal cancer (CRC) patients. Primary tumour tissues of 41 KRAS wild-type mCRC patients receiving cetuximab-based chemotherapy were investigated for PI3K, PTEN, KRAS and BRAF mutations. Progression-free survival (PFS) and overall survival (OS) periods were calculated with Kaplan-Meier method and the Cox proportional hazards model was used. PTEN and PI3K expressions were 63 and 42 %, respectively. BRAF mutation was observed as 9.8 % among patients. Tumours with BRAF mutation had statistically lower response rates (RR) for cetuximab-based treatment than tumours with BRAF wild type (0 vs. 58 %, p = 0.02). PTEN expressing tumours had statistically higher RR for cetuximab-based treatment than tumours with PTEN loss (42 vs. 12 %, p = 0.04). PI3K expression had worse significant effect on cetuximab RR than PI3K non-expressed tumours (15 vs. 44 %, p = 0.023). Median PFS was significantly longer in patients with PTEN expression (14 months) than in patients with PTEN loss (5 months) (HR, 0.4; p = 0.028). Median PFS was significantly longer in patients with PI3K non-expression (15.2 months) than in patients with PI3K expression (4.1 months) (HR, 0.31; p = 0.001). Significant difference in PFS and OS between patients with BRAF mutated and BRAF wild-type tumours was not detected. However, patients with PTEN expression had significantly longer OS (15.1 months) than patients with PTEN loss tumour (9.9 months) (HR, 0.34; p = 0.008). Patients without PI3K expression had significantly longer OS (18.2 months) than patients with PI3K expression (10.1 months) (HR, 0.27; p = 0.001). Multivariate analyses revealed that PTEN expression (HR, 0.48; p = 0.02) and absence of PI3K expression (HR, 0.2; p = 0.001) were independent prognostic factors for increased PFS. Similarly, PTEN overexpression (HR, 0.62; p = 0.03) and absence of PI3K expression (HR, 0.27; p = 0.005) were independent prognostic factors for increased OS. In PTEN loss, PI3K expression may be used as biomarkers to further select KRAS wild-type patients undergoing anti-epidermal growth factor receptor treatment.

Gastrointestinal stromal tumors in Turkey: experiences from 3 centers.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal system. The most common primary site of GIST is the stomach. The treatment is primarily surgery, and the standard medical therapy is imatinib. Long-term survival can be obtained with good follow-up and treatment. MATERIALS AND METHODS: In this study, data entry was performed using a web-based patient registry system for patients who were referred to 3 centers and retrospectively were diagnosed with GIST. RESULTS: The study cohort consisted of 249 patients, including 160 men (64.3%) and 89 women (35.7%). The mean age was 59 years (range 21-90 years). Initially, 69.9% of the patients had local disease, while 30.1% had metastatic disease. The tumor was located in the stomach in 45.6% of patients. According to the Fletcher risk classification, the very low risk group included 8 subjects (3.2%), the low risk group included 40 subjects (16.1%), the moderate risk group included 56 subjects (22.5%), and the high risk group included 117 subjects (47%); the unspecified group included 28 subjects (11.5%). CONCLUSION: These data are important for revealing the clinicopathologic characteristics and survival data of patients with GIST, who are treated and followed up in Turkey.

Association KRAS G13D tumor mutated outcome in patients with chemotherapy refractory metastatic colorectal cancer treated with cetuximab.

BACKGROUND/AIMS: Cetuximab is currently approved for the treatment of metastatic colorectal cancer (mCR) with KRAS wild-type. Prior few studies demonstrated that G13D mutated tumors could benefit from cetuximab. This study aims to investigate whether KRAS G13D mutated tumors benefit from cetuximab in the chemotherapy refractory patients. METHODOLOGY: We retrospectively compared progression-free survival (PFS), overall survival (OS) and response rate (RR) according to KRAS mutation status in 105 patients with mRC treated at the Cerrahpasa Medical School Hospital, between October 2008 and October 2011, with cetuximab alone or in combination with chemotherapy. RESULTS: PFS was significantly longer in patients G13D mutated tumors (6.81 months) than in patients with other KRAS mutated tumors (5 months) (p=0.027). No significant difference in PFS between patients G13D mutated and KRAS wild-type tumors was detected. No significant difference in OS was detected in patients between G13D mutated tumors and other KRAS mutated tumors. However, patients with KRAS wild-type tumors had significantly longer OS (16.1 months) than patients with mutated tumors (8.9 months) (p=0.025). RR in patients with other KRAS mutated tumors, was significantly worse than those with G13D mutated tumors (p=0.002). CONCLUSION: Our study demonstrated an association between the presence KRAS G13D mutanted and survival chemotherapy in refractory metastatic colorectal cancer treated with cetuximab.

Port-related Delftia tsuruhatensis bacteremia in a patient with breast cancer.

Delftia tsuruhatensis is a non-glucose fermenting, oxidase positive, motile, gram-negative bacillus first isolated from activated sludge collected from a domestic wastewater treatment plant in Japan. To the best of our knowledge only one case of infection with Delftia tsuruhatensis exists in the medical literature. This is the second case report of human infection having Delftia tsuruhatensis as a causative agent.

Radioligand Therapy With 177 Lu-PSMA-I&T in Patients With Metastatic Prostate Cancer : Oncological Outcomes and Toxicity Profile.

INTRODUCTION: This study aimed to investigate the oncological outcomes and toxicity profile of 177 Lu-PSMA-I&T radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as our initial experience in metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS: A total of 38 consecutive patients with metastatic prostate cancer (33 mCRPC and 5 mHSPC) received 177 Lu-PSMA-I&T RLT, with a median of 2 cycles per patient (range, 1-7). Response to RLT was evaluated based on prostate-specific antigen (PSA) changes and imaging response. Clinical progression-free survival and overall survival were used to report oncological outcomes. Toxicity was assessed using the Common Toxicity Criteria for Adverse Events criteria. RESULTS: In mCRPC, 22 (69%), 18 (56%), and 11 (34%) patients achieved any PSA decline, PSA response of ≥30%, and PSA response of ≥50%, respectively. The clinical progression-free survival and overall survival after the first cycle of RLT were 6.3 and 21.4 months, respectively. In mHSPC, 177 Lu-PSMA-I&T RLT resulted in excellent PSA response (93.0%-99.9%) in all cases. Clinical progression and cancer-related mortality occurred in only 1 case. Toxicity profile was favorable in both mHSPC and mCRPC. CONCLUSIONS: 177 Lu-PSMA-I&T RLT demonstrated favorable PSA response (≥30%) in over half of the patients with mCRPC and excellent PSA response in all patients with mHSPC. Toxicity profile was favorable in both mHSPC and mCRPC settings. Further studies are needed to evaluate the role of 177 Lu-PSMA-I&T RLT in the management of metastatic prostate cancer.

Optimizing the Personalized Care for the Management of Rectal Cancer: A Consensus Statement.

Colorectal cancer is the third most common cancer in Turkey. The current guidelines do not provide sufficient information to cover all aspects of the management of rectal cancer. Although treatment has been standardized in terms of the basic principles of neoadjuvant, surgical, and adjuvant therapy, uncertainties in the management of rectal cancer may lead to significant differences in clinical practice. In order to clarify these uncertainties, a consensus program was constructed with the participation of the physicians from the Acibadem Mehmet Ali Aydinlar and Koç Universities. This program included the physicians from the departments of general surgery, gastroenterology, pathology, radiology, nuclear medicine, medical oncology, radiation oncology, and medical genetics. The gray zones in the management of rectal cancer were determined by reviewing the evidence-based data and current guidelines before the meeting. Topics to be discussed consisted of diagnosis, staging, surgical treatment for the primary disease, use of neoadjuvant and adjuvant treatment, management of recurrent disease, screening, follow-up, and genetic counseling. All those topics were discussed under supervision of a presenter and a chair with active participation of related physicians. The consensus text was structured by centralizing the decisions based on the existing data.

The real-life efficacy and safety of osimertinib in pretreated advanced non-small cell lung cancer patients with T790M mutation: a Turkish Oncology Group Study.

INTRODUCTION: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose disease progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation. MATERIALS AND METHODS: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety. RESULTS: Of 163 patients, 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13-month follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients. CONCLUSION: Osimertinib is a highly effective option in second- or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile.

Efficacy and safety of folfiri plus aflibercept in second-line treatment of metastatic colorectal cancer: Real-life data from Turkish oncology group.

Aims: The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience. Materials and Methods: Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed. Results: The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity. Conclusions: Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial.

Bisphosphonate-related osteonecrosis: laser-assisted surgical treatment or conventional surgery?

Bisphosphonates (BSPs) are used for the treatment of multiple myeloma, metastatic breast and lung cancer, Paget's disease, osteoporosis, hypercalcemia due to malignancy, and many other skeletal diseases. BSPs reduce osteoclastic functions, which result in bone resorption. Bisphosphonates-related osteonecrosis of jaws (BRONJ) is a newly developed term that is used to describe the significant complication in patients receiving bisphosphonates. BSPs are known to exhibit an anti-angiogenetic effect that initiates tissue necrosis of the hard tissue. There is currently no consensus on the correct approach to this issue. The aim of this retrospective study is to compare the effects of laser surgery with biostimulation to conventional surgery in the treatment of BSP-induced avascular bone necrosis on 20 patients who have been treated in our clinic. BRONJ was evaluated in patients with lung, prostate, and breast cancer under intravenous BSP treatment. Twenty patients in this study developed mandibular or maxillary avascular necrosis after a minor tooth extraction surgery or spontaneously. Bone turnover rates were evaluated by serum terminal C-telopeptide levels (CTX) using the electrochemiluminescence immunoassay technique and patients were treated with laser or conventional surgical treatments and medical therapy. Ten patients were treated with laser surgery and biostimulation. An Er:YAG laser (Fotona Fidelis Plus II® Combine laser equipment, Slovenia) very long pulse (VLP) mode (200 mJ, 20 Hz) using a fiber tip 1.3 mm in diameter and 12 mm in length was used to remove the necrotic and granulation tissues from the area of avascular necrosis. Biostimulation was applied postoperatively using an Nd:YAG laser. Low-level laser therapy (LLLT) was applied to the tissues for 1 min from 4 cm distance using an Nd:YAG laser (Fotona-Slovenia) with a R24 950-µm fiber handpiece long-pulse (LP) mode, 0.25-W, 10 Hz power/cm(2) from the mentioned distance the spot size was 0.4 cm(2), and power output was 2.5 J. Energy density from the mentioned distance was calculated to be 6.25 J/cm(2). The other ten patients were treated with conventional surgery. Treatment outcomes were noted as either complete healing or incomplete healing. There were no statistically significant differences between laser surgery and conventional surgery (p > 0.05). CTX values also did not affect the prognosis of the patients. Treatment outcomes were significantly better in patients with stage II osteonecrosis than in patients with stage I osteonecrosis. Our findings suggest that dental evaluation of the patients prior to medication is an important factor in the prevention of BRONJ. Laser surgery is a beneficial alternative in the treatment of patients with this situation. Further randomized studies with larger patient numbers may also improve our understanding of treatment protocols for this situation.

The prediction of spread through air spaces with preoperative 18F-FDG PET/CT in cases with primary lung adenocarcinoma, its effect on the decision for an adjuvant treatment and its prognostic role.

PURPOSE: In lung adenocarcinoma cases, 'spread through air spaces' (STAS) is a new indicator of invasion and directly related to disease survival. The aim of our study is to establish whether a preoperatively performed 18F-Fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging data can predict the presence of STAS in cases with lung adenocarcinoma and thus predict the decision for the type of surgery and adjuvant chemotherapy. MATERIALS AND METHODS: Between 2000 and 2019, we retrospectively analyzed 63 patients with lung adenocarcinoma cases that had undergone lobectomy or pneumonectomy. Semiquantitative parameters were calculated and metabolic tumor volume (MTV)/CT volume (CTV) ratio was recorded from FDG PET/CT data. The pathological samples from these patients were evaluated for STAS. All these values were evaluated for their correlation with the alveolar spread. RESULTS: There was no statistically significant correlation to be found between CTV, MTV, total lesion glycolysis (TLG), standardized uptake value (SUV)max, SUVmean and STAS (P > 0.05). However, MTV/CTV ratio above 1 had statistically more alveolar spread. In the group with an MTV ratio above 1, STAS positivity was 27 (75%), and 9 (25%) did not have STAS, whereas these were 6 (22.2%) patients who had STAS, and 21 (77.8%) did not have STAS in the group with below 1 (P < 0.001). CONCLUSIONS: In the preoperative PET study inoperable lung adenocarcinoma cases, MTV/CTV ratio higher than 1 was found to predict STAS positivity. As a result, it was found that it provided significant clinical additional information regarding the need for a surgical approach (lobar resection instead of sublobar) and adjuvant chemotherapy.

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

Level of pleural invasion effects on prognosis in lung cancer.

OBJECTIVE: To analyze the extent of visceral pleural invasion (VPI) and its effect on survival along with its place in determining the T descriptor in TNM staging in our patients. METHODS: A total of 233 patients underwent lung resection. The data were retrospectively analyzed in terms of sex, age, histopathologic type, stage of the tumor, extent of VPI, and survival. Patients who had neoadjuvant chemotherapy or chemoradiotherapy, distant metastasis, parietal pleural invasion, and operative mortality were excluded. RESULTS: The median follow-up was 59 months (range 4-126). The extent of VPI was PL0 in 119 (65.7%) patients, PL1 in 47 (26%) patients, and PL2 in 15 (8%) patients. The median survival rates were 65 (range 43-96) months for PL0, 54 (range 37-72) months for PL1, and 39 (range 12-69) months for PL2. The 5-year overall survival rates were 74.7% for PL0, 77.8% for PL1, and 53.3% for PL2. There were statistically significant differences in overall survival among PL0, PL1, and PL2 ( p = 0.03). In subgroup analysis, the difference was insignificant in PL0 vs PL1 ( p = 0.81), but significant in PL0 vs PL2 ( p = 0.02) and PL1 vs PL2 ( p = 0.04) groups. CONCLUSIONS: This study emphasizes that the presence of VPI is related with poor prognosis independent of lymph node positivity, histologic subtypes, and tumor size. As the study shows, PL0 and PL1 have similar survival rates and these two groups may be considered as VPI (-) patients whereas PL2 disease affects survival outcomes.

Nutritional Aspect of Cancer Care in Medical Oncology Patients.

PURPOSE: Awareness of advances in the nutritional aspects of cancer care and translation of this information into clinical practice are important for oncology practitioners to effectively couple oncologic and nutritional approaches throughout the cancer journey. The goal of this consensus statement by a panel of medical oncologists was to provide practical and implementable guidance addressing nutritional aspects of cancer care from the perspective of the medical oncologist. METHODS: A panel of medical oncologists agreed on a series of statements supported by scientific evidence and expert clinical opinion. FINDINGS: Participating experts emphasized that both poor nutritional intake and metabolic alterations underlie cancer-related malnutrition. The use of liquid and high energy-dense oral nutritional supplements may enable better patient compliance, whereas higher efficacy is more likely with the use of pharmaconutrient-enriched oral nutritional supplements in terms of improved weight, lean body mass, functional status, and quality of life, as well as better tolerance to antineoplastic treatment. A multimodal approach is currently believed to be the best option to counteract the catabolism leading to cancer-related malnutrition; this treatment is scheduled in parallel with anticancer therapies and includes nutritional interventions, multitarget drug therapies, and exercise and rehabilitation programs. Participating experts emphasized the role of the oncologist as a reference professional figure in the coordination of nutritional care for patients with cancer within the context of complex and different clinical scenarios, particularly for permissive-adjunctive nutritional support. IMPLICATIONS: This review article provides practical guidance addressing major nutritional aspects of cancer care from the medical oncologist's perspective. Thus, this document is expected to assist oncology practitioners in terms of awareness of advances in the nutritional aspects of cancer care and translation of this information into their clinical practice to effectively couple oncologic and nutritional approaches as part of the continuum of care for patients with cancer.

Implementation of an antimicrobial stewardship program for patients with febrile neutropenia.

BACKGROUND: We aimed to describe the effectiveness of our standardized protocol for febrile neutropenia (FN), which was targeted to minimize unintended outcomes and reduce antimicrobial consumption. METHODS: The study was performed in a private hospital with 300 beds. We included all adult hematologic and oncologic cancer inpatients admitted between January 1, 2015-December 31, 2015, and January 1, 2016-May 31, 2017. The outcomes of the study were fatality, infections, and adherence to the antimicrobial stewardship program (ASP). RESULTS: We included 152 FN attacks of 95 adult inpatients from hematology and oncology wards; of these, 43% were women, and the median age was 57 years. The case fatality rate was 30% in the pre-ASP period and decreased to 11% in the post-ASP period (P = .024). The appropriate adding or changing (P = .006) and appropriate continuation or de-escalation or discontinuation of antimicrobials improved (P < .001). In the post-ASP period, Staphylococcus spp infections (from 22% to 8%, P = .02) and gram-negative infections decreased (from 43% to 20%, P = .003). In the multivariate analysis, appropriate continuation or de-escalation or discontinuation was increased in the post-ASP period (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.82-10.41; P = .001), and gram-positive infections were decreased (OR, 0.32; 95% CI, 0.11-0.95, P = .041). Vancomycin and fluoroquinolone use decreased significantly. CONCLUSIONS: After implementation of the ASP, the case fatality rate among the patients with FN decreased. Appropriate antimicrobial use increased and overall antimicrobial consumption was reduced. Bacterial infections and Candida infections decreased.

The role of US and MR imaging in detecting local chest wall tumor recurrence after mastectomy.

PURPOSE: To determine the role of clinical examination, ultrasonography (US), and magnetic resonance imaging (MRI) in detecting local tumor recurrence in patients who underwent modified radical mastectomy for breast cancer. MATERIALS AND METHODS: The study included 27 patients who were examined between April 1999 and April 2003. US evaluation of the chest wall was performed in all patients. MRI was performed on 10 patients due to suspicious findings in clinical examination, on 3 patients due to US findings, and on 8 patients due to both US and clinical examination findings. Six patients without any suspicious findings underwent MRI for follow-up purposes. The lesions detected with MRI were evaluated according to their morphology, contrast enhancement characteristics and dynamics. The focal lesions that enhanced intensely at the early phase were accepted as suspicious for malignancy. RESULTS: Of the 10 cases that underwent biopsy secondary to suspicious lesions for malignancy according to MRI findings, 7 were found to have recurrence. In the remaining 3 patients, recurrence diagnosis was made based on the fact that the lesions regressed in response to chemotherapy. In 17 cases, there were no suspicious findings on MRI for local recurrence. In 2 of these cases, biopsies were performed due to suspicious US findings; however, no malignancies were detected. The sensitivity and specificity of clinical examination in detecting local recurrence was 70% and 35.2%, respectively. These values were 90% and 88.2% for US, and 100% and 100% for MRI. CONCLUSION: In patients with mastectomy, US and MRI were more successful in detecting local recurrence than clinical examination. Considering the fact that US is cheaper and more readily available than MRI, it should be part of the routine follow-up in order to detect local recurrence early. MRI will be helpful in cases with suspicious US findings by increasing the specificity of the evaluation as well as determining the actual size and spread of any lesions, which is valuable information for the subsequent management and response to the particular treatment.

The correlation of angiogenesis with metastasis in primary cutaneous melanoma: a comparative analysis of microvessel density, expression of vascular endothelial growth factor and basic fibroblastic growth factor.

AIM: To establish whether there is a correlation between angiogenesis and metastasis in primary cutaneous melanoma (PCMM). METHODS: We studied the microvessel density and the expression of vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) in 22 cases of PCMM with metastasis at presentation (metastatic group) and 28 cases of PCMM without metastasis for 24 months or more (non-metastatic group). Microvessels were stained with CD31/PECAM-1 antibody and counted. We assessed the proportion of VEGF expression in tumour cells, lymphocytes infiltrating the tumour (TIL) and lymphocytes at the periphery of the tumour, as well as the proportion of bFGF expression in tumour cell cytoplasms, nuclei and intra- and peritumoral vessels. RESULTS: An increased microvessel density was detected in the metastatic group (15-33 [24.09 +/- 5.55] versus 2-24 [12.96 +/- 6.02]). Moreover, enhanced expression of VEGF in tumour cells and peritumoral lymphocytes (Chi-square p = 0.038 and p = 0.018) and bFGF in peritumoral vessels (chi(2) p = 0.013) correlated with the simultaneous presence of melanoma metastasis in PCMM. Furthermore, microvessel density was correlated with the expression of bFGF in peritumoral vessels (rs = 0.53, p = 0.049) and VEGF in tumour cells (rs = 0.37, p = 0.019). CONCLUSION: Microvessel density as well as the expression of both VEGF and bFGF might be informative concerning the progression of melanoma.