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.

Frequency of germline pathogenic variants in breast cancer predisposition genes among young Turkish breast cancer patients.

PURPOSE: One of the most important risk factors for hereditary breast and ovarian cancer is young age. We aim to report the frequency of pathogenic/likely pathogenic variants in breast cancer predisposing genes in young (≤ 40 years old) breast cancer patients who undergone 26-gene inherited cancer panel at our Breast Health Center. METHODS: Medical records of breast cancer patients who were referred to genetic counseling based on NCCN criteria and were ≤ 40 years of age are reviewed. The frequency of germline pathogenic/likely pathogenic variants who undergone 26-gene inherited cancer panel was analyzed. RESULTS: Among 414 breast cancer patients who were ≤ 40 years of age, 308 undergone 26-gene inherited cancer panel and 108 had next generation sequencing (NGS)-based BRCA 1 and 2 genetic testing. Median age was 35 (22-40), Family history in first degree relatives was present in 14% of patients. Forty-five percent of patients met one of the NCCN criteria for genetic testing, 41% of them met two criteria, and 14% of patients fulfilled ≥ 3 criteria. Seventy pathogenic/likely pathogenic variants (PV/LPV) were found in 65 (21%) patients. PV/LPs in BRCA genes and non-BRCA genes represented 53% and 44% of all PV/LPVs, accounting for 12% and 10% of patients in the study cohort respectively. Two PVs were present in 5 patients and eleven PVs were novel. The most common PVs were in BRCA 1 (n:18), BRCA 2 (n:19), ATM (n:7), CHEK2 (n:7) and TP53 (n:5) genes. Thirty-one percent of the patients with triple-negative tumors and 25% of the patients with hormone receptor-positive tumors had PV/LPVs with panel testing. Family history in first degree relatives (p = 0.029), the number of met NCCN criteria (p = 0.036) and axillary nodal involvement (p = 0.000) were more common in patients with PVs. When combined with patient group (n:106) who had only BRCA1 and 2 gene testing, 16% of Turkish breast cancer patients ≤ 40 years of age had PVs in BRCA genes. CONCLUSION: One fifth of Turkish breast cancer patients ≤ 40 years of age had at least one PV/LPV in breast cancer predisposing genes with 26-gene inherited cancer panel. The frequency of PV/LPVs was higher in triple-negative young-onset patients compared to hormone receptor and Her-2 positive subtypes. Our findings regarding to frequency PV/LPVs in BRCA 1/2 and non-BRCA genes in young-onset breast cancer patients are in line with the literature.

Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.

AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

Alpelisib induced interstitial lung disease in a patient with advanced breast cancer.

BACKGROUND: Interstitial lung disease interstitial lung disease is a group of respiratory diseases that causes progressive fibrosis. Many of the recently approved oncology drugs are associated with the development of interstitial lung disease as an adverse event. We report an alpelisib-induced interstitial lung disease in a patient with advanced breast cancer. CASE REPORT: A 65-year-old breast cancer patient who had multiple bone metastases and had been previously treated with letrozole and ribociclib, started alpelisib and fulvestrant combination upon the development of liver metastases. Her past medical history was not significant except the history of hypertension. She developed fatigue and progressive dyspnea 3, 5 months after starting alpelisib and was hospitalized due to rapidly deteriorating hypoxia within 2-3 days. MANAGEMENT AND OUTCOME: Naranjo Algorithm calculated score was 4 (probable Adverse Drug Reaction). Her thoracic computed tomography and angiography scan were consistent with interstitial infiltrate ground-glass appearance. She had no fever. Her workup for COVID-19 (coronavirus disease), other respiratory infectious agents, and pulmonary embolism was negative. There was a rapid clinical and radiologic response to corticosteroid therapy within one week. She was discharged from the hospital with a tapered steroid dose and complete resolution of her lung infiltrations. Alpelisib was discontinued despite radiological partial response in her liver metastases and a decline in her tumor marker. DISCUSSION: Drug-induced interstitial lung disease is usually a diagnosis of exclusion, difficult to identify particularly during the COVID-19 pandemic for patients with cancer. Differential diagnosis includes infectious pneumonia, radiation pneumonitis, diffuse alveolar hemorrhage, pulmonary edema, and pulmonary lymphangitic metastasis.

Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study.

PURPOSE: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings. METHODS: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. RESULTS: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). CONCLUSION: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

The Relationship Between Body Composition and Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

Background The pathological response rate in operable breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC) is postulated to be related to body composition. The success of complete pathological response (pCR) is a known prognostic factor in BC patients treated with NAC. We aimed to accurately measure body composition through BMI and skeletal muscle mass and observe their effects on pCR. Materials and methods Patients diagnosed with operable BC who had a positron emission tomography-computed tomography (PET-CT) or chest/abdominal CT taken at the time of diagnosis were retrospectively screened and enrolled in this study. Muscle mass was defined by third lumbar vertebra (L3) level transverse CT images, and data, including weight and height, were collected from the chemotherapy records. All these data were evaluated together with the postoperative pathological results. Results Sixty-nine operable BC patients with a median age of 46 (range: 29-72) years were included in the study. In all patients, regardless of sarcopenia, 23% (n = 16) achieved pCR to NAC. The pCR rate was 37.5% (n=6) in sarcopenic patients and 62.5% (n=10) in non-sarcopenic patients (p = 0.530). Overweight (n=4; 25%) and obese (n=2; 12.5%) patients also had a lower pathological response than normal-weight (n=10; 62.5%) BC patients (p=0.261). Conclusion Both sarcopenia and obesity independently and synergistically contribute to poorer pathological responses after NAC. Addressing these conditions through tailored interventions, such as nutritional support, exercise programs, and careful monitoring of body composition, could improve treatment outcomes. Further research with larger patient populations and comprehensive body measurements is essential to fully understand these relationships and develop effective strategies to mitigate their impact.

Recommendations for cyclin­dependent kinase 4/6 inhibitor treatments in the context of co­morbidity and drug interactions (Review).

Breast cancer is most frequently diagnosed among women aged 65-74 years and the prevalence of comorbidities in elderly patients with breast cancer is 32.2%. In addition, polypharmacy is quite common in these patients. Understanding the interaction between breast cancer treatment modalities and comorbidities is important, particularly in elderly patients, as comorbidities affect the choice of appropriate treatment and are independent risk factors for survival. A total of three oral cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), palbociclib, ribociclib and abemaciclib, notably prolonged progression-free survival when combined with endocrine therapy (ET), compared with ET alone in patients with advanced breast cancer (ABC). The present review article therefore addressed the safety, tolerability and toxicity of CDK4/6i treatment in ABC management, compiled real-world data on how multiple clinical and pharmacological features may affect the choice of these drugs and provided practical recommendations for clinical approaches. Before starting treatment with CDK4/6i drugs, all ongoing medical conditions should be inventorized and re-graded, and examination should be performed for any additional disease that the patient may not be aware of. It is also important to obtain a detailed history of concomitant drugs, including prescription and over-the-counter drugs, vitamins, supplements and herbal products. In addition, patients should be advised to consult their oncologist before starting any new medication.

Real-world data on the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab: Turkish oncology group multicenter study.

We aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 - 12.2); this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) (p = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line(p = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.

Serum thymidine kinase 1 levels correlates with FDG uptake and prognosis in patients with non small cell lung cancer.

CONTEXT: TK1 found to be elevated biomarker in many solid cancers. OBJECTIVES: The study aimed to assess the prognostic significance of a serum TK1 in patients with metastatic NSCLC. METHODS: The study included 48 consecutive patients, newly diagnosed with metastatic NSCLC, and 10 healthy volunteers. Serum TK1 activity determined by ELISA method. RESULTS: Patients with a bTK1 level >156 Du L(-1) had significantly shorter survival. TK1 level showed a strong correlation with primary tumor SUV(max). DISCUSSION AND CONCLUSION: The magnitude of maximum fluorodeoxyglucose uptake in primary tumors and the serum TK1 level in patients with metastatic NSCLC were found to be independent prognostic predictors of overall survival.

Demographic and Clinical Features of Patients with Metastatic Breast Cancer: A Retrospective Multicenter Registry Study of the Turkish Oncology Group.

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0-55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.

What Has Changed in Patients Aged 65 and over Diagnosed with Breast Cancer during the COVID-19 Pandemic: A Single-Center Experience.

Introduction: The COVID-19 pandemic has a worldwide negative impact on healthcare systems. This study aims to determine how the diagnosis, clinicopathological features, and treatment approaches of patients with breast cancer (BC) diagnosed at ≥65 years old were affected during the pandemic. This survey has shown that patients, especially the elderly, had to postpone their BC health problems or delay their routine controls due to the risk of COVID-19 transmission, high mortality rates due to comorbidity, and restrictions. Materials and Methods: The medical records of 153 patients with BC diagnosed at ≥65 years old before (January-December 2019; group A, n = 61) and during (March 2020-May 2021; group B, n = 92) the COVID-19 pandemic were retrospectively analyzed. In addition, clinicopathological features of patients, including age, admission form, clinical stage, tumor (T) size-grade-histology-subtype, lymph node involvement, surgery type, and treatment protocols, were evaluated. Results: Patients mostly applied for screening purposes were included in group A and patients who frequently applied for diagnostic purposes due to their existing BC or other complaints were included in group B (p = 0.009). Group B patients had a higher clinical stage (p = 0.026) and had commonly larger (p = 0.020) and high-grade (p = 0.001) Ts. Thus, mastectomy and neoadjuvant systemic therapy were more commonly performed in group B (p = 0.041 and p = 0.005). Conclusion: The survey showed significant changes in BC diagnosis and treatment protocols for patients diagnosed at ≥65 years old during the COVID-19 pandemic. Postponing screening and delaying treatment leads to more advanced BC stages in elderly patients.

How Do Breast Cancer Patients Present Following COVID-19 Early Peak in a Breast Cancer Center in Turkey?

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has placed an unprecedented burden on healthcare systems and restricted resources for non-COVID patients worldwide. Treatment approaches and follow-up plans have been modified to prevent the risk of infection for patients and healthcare workers. Patients prefer to delay or cancel their treatments during the peak period of infection. MATERIALS AND METHODS: We retrospectively reviewed the characteristics of patients with breast cancer who were consulted at our outpatient clinic right after early COVID-19 peak in May and June 2020 and compared them with the same period in 2017 to 2019. RESULTS: The number of patients who consulted at our outpatient medical oncology clinic declined in May and June 2020. This decline was regardless of stage and was larger in May than in June 2020. In general, the distribution of tumor subtypes [luminal, human epidermal growth factor receptor 2 (HER-2) positive, and triple negative] was not different from 2017 to 2020. Less than half of the patients received adjuvant chemotherapy following early COVID-19 peak in May and June 2020. Few patients received chemotherapy for metastatic disease, whereas many metastatic patients received endocrine therapy. None of the consulted new patients had a non-invasive disease. More patients received endocrine therapy than chemotherapy. CONCLUSION: The presentation patterns of patients with breast cancer after early COVID-19 peak differed from those during the same period in the last 3 years. The pandemic affected the number of new patients consulted and the way medical oncologists treat their patients.

Turkish national consensus on breast cancer management during temporary state of emergency due to COVID-19 outbreak.

OBJECTIVES: Cancer care is excessively influenced by the COVID-19 outbreak for various reasons. One of the major concerns is the tendency for delayed surgical treatment of breast cancer patients. The outbreak has urged clinicians to find alternative treatments until surgery is deemed to be feasible and safe. Here in this paper, we report the results of a consensus procedure which aimed to provide an expert opinion-led guideline for breast cancer management during the COVID-19 outbreak in Turkey. MATERIAL AND METHODS: We used the Delphi method with a 9-scale Likert scale on two rounds of voting from 51 experienced surgeons and medical oncologists who had the necessary skills and experience in breast cancer management. Voting was done electronically in which a questionnaire-formatted form was used. RESULTS: Overall, 46 statements on 28 different case scenarios were voted. In the first round, 37 statements reached a consensus as either endorsement or rejection, nine were put into voting in the second round since they did not reach the necessary decision threshold. At the end of two rounds, for 14 cases scenarios, a statement was endorsed as a recommendation for each. Thirty-two statements for the remaining 14 were rejected. CONCLUSION: There was a general consensus for administering neoadjuvant systemic therapy in patients with node-negative, small-size triple negative, HER2-positive and luminal A-like tumors until conditions are improved for due surgical treatment. Panelists also reached a consensus to extend the systemic treatment for patients with HER2-positive and luminal B-like tumors who had clinical complete response after neoadjuvant systemic therapy.

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.

The association between individual attachment patterns, the perceived social support, and the psychological well-being of Turkish informal caregivers.

BACKGROUND: This study aimed to investigate the relations among the psychological well-being (i.e. depression and state/trait anxiety levels), attachment patterns (i.e. secure, ambivalent, avoidant), and the perceived social support from family/friends/significant others of caregivers of cancer patients in Turkey. METHODS: Fifty-one caregivers of adult cancer patients were recruited from the oncology outpatient clinic of the Marmara Medical School Hospital in Istanbul. Caregivers were assessed with the Adult Attachment Scale, the Beck Depression Inventory, State-trait Anxiety Inventories, and the Multidimensional Scale of Perceived Social Support. RESULTS: Stepwise multiple regression analysis indicated that depression was predicted by ambivalent attachment and the perceived social support from family. The support from significant others was the significant predictor of trait anxiety and the caregivers' ambivalent attachment score was the significant predictor of state anxiety. CONCLUSIONS: We assert that ambivalent attachment pattern could confer a vulnerability to psychological distress in cancer caregivers. Assessing the psychological experiences and needs of caregivers and being aware of possible risk factors (such as attachment patterns) and protective factors (social support network) for depression and anxiety might be helpful for successful programmes and interventions that support the caregivers of cancer patients.

Anti-tumor activity of capecitabine and vinorelbine in patients with anthracycline- and taxane-pretreated metastatic breast cancer: findings from the EORTC 10001 randomized phase II trial.

The aim of this randomized phase II study was to evaluate the anti-tumor activity and safety of capecitabine and vinorelbine in patients with metastatic breast cancer pretreated with taxanes and anthracyclines. We planned to randomize 72 patients to capecitabine 1250 mg/m(2) orally bid days 1-14 or vinorelbine 30 mg/m(2) i.v. days 1 and 8, both given every 3 weeks. The study was stopped due to poor accrual with 47 patients enrolled. Responses were seen in 2/23 patients treated with capecitabine (8.7%; 95% CI 1.1-29.0) and 3/24 patients treated with vinorelbine (12.5%; 95% CI 2.7-32.4). Median progression-free survival was 2.8 and 2.6 months, and median overall survival was 9.3 and 11.0 months, in the capecitabine and vinorelbine arms, respectively. There was more hematologic toxicity, neurotoxicity, and nausea/vomiting with vinorelbine and more diarrhea and hand-foot syndrome with capecitabine. The anti-tumor activity of capecitabine and vinorelbine seems to be comparable, but the toxicity profiles are different.

Ongoing unmet needs in treating estrogen receptor-positive/HER2-negative metastatic breast cancer.

Estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer (MBC) is the most common MBC subtype and currently remains incurable, with a median overall survival of 24.8 months (95% confidence interval, 21.3-30.3). Common sites of metastases are bone, viscera, and brain, causing significant symptoms that negatively affect patient functioning, quality of life (QoL), and work productivity. Guidelines state that endocrine therapy (ET) is preferable to chemotherapy as first-line treatment for patients with ER+ MBC, regardless of limited visceral metastases, unless rapid tumor response is required or ET resistance is suspected. Although response rates up to 40% have been reported for first-line MBC treatment, the majority of initial responders eventually develop ET resistance. Notwithstanding the steep decline in efficacy between first and later lines of ET, some patients may receive chemotherapy earlier than necessary. Although new treatments have been approved for patients with ER+/HER2- advanced or MBC in the past decade, neither survival nor QoL appear to have improved significantly. Thus, there remain significant unmet needs for this patient population, including improved survival, maintaining or improving patient QoL, and emphasizing the importance of treatment selection to assist healthcare practitioners managing patient care. In this review, we identify current challenges and unmet needs in this patient population, review cutting-edge treatments, and provide clinically relevant suggestions for treatment selection that can optimize outcomes and patients' health-related QoL.

Epithelioid hemangioendothelioma with multiple organ involvement.

Epithelioid hemangioendothelioma is a rare vascular neoplasm of uncertain malignant potential. Various reports document metastatic or concurrent epithelioid hemangioendothelioma in several sites, most commonly with combined lung and liver involvement. The concurrent involvement of multiple sites at presentation may cause diagnostic problems because epithelioid hemangioendothelioma can mimic other neoplastic processes. Although it is a chemo-resistant disease, chemotherapy is usually advised for patients with metastatic or concurrent involvement. Here we document the presentation, treatment, and outcome of two cases with concurrent involvement of the lung and liver.

Vascular endothelial growth factor, hypoxia-inducible factor 1 alpha and CD34 expressions in early-stage gastric tumors: relationship with pathological factors and prognostic impact on survival.

BACKGROUND: Angiogenesis is one of the key steps in solid tumor growth and metastasis. We planned to investigate the prognostic significance of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1alpha (HIF-1alpha) and CD34 expressions as markers of angiogenesis in gastric cancer. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 51 gastric cancer patients who had total or subtotal gastrectomy at Marmara University Hospital from 1990 to 2004 and evaluated the expression of VEGF, HIF-1alpha and CD34 by immunohistochemistry in their archival tumor tissues. We recorded the clinical and pathological characteristics of these patients and analyzed their survival outcome. RESULTS: Thirty out of 51 patients were males. The median age was 63 years (range 34-81). The median follow-up was 17 months. Thirty-six patients had node-positive disease. The majority of patients (n = 43) had T2 and T3 disease. Vascular and lymphatic invasions were present in 57 and 77% of tumors, respectively. VEGF and HIF-1alpha were positive in 65 and 71% of tumors. The median CD34 staining score was 19 (3-68). VEGF, HIF-1alpha and CD34 expressions were more frequent in tumors without serosal invasion (p = 0.01, p = 0.01 and p = 0.003, respectively). CD34 expression was significantly more frequent in tumors with VEGF and HIF-1alpha expression (p = 0.00, p = 0.00). HIF-1alpha expression was more frequent in tumors with VEGF expression (p = 0.00). The 5-year overall survival was 45%. VEGF, HIF-1alpha, CD34 expressions and other pathological characteristics were found to have no impact on survival. CONCLUSION: VEGF, HIF-1alpha and CD34 expressions were more common in tumors without serosal invasion. As a future perspective, biological agents targeting VEGF and HIF-1alpha might be more effective at earlier stages of gastric cancer.