The Relationship between Exercise Capacity and Muscle Strength, Physical Activity, Fatigue and Quality of Life in Patients with Cancer Cachexia.

BACKGROUND: Exercise capacity is a significant determinant of mortality for cancer patients, so knowing the possible determinants of exercise capacity will produce physical and psychological benefits for individuals with cancer cachexia. PURPOSE: To investigate the relationship between exercise capacity on peripheric and respiratory muscle strength, physical activity, fatigue and quality of life in subjects with cancer cachexia. METHODS: The study included 31 patients diagnosed with cancer cachexia. Functional capacity was assessed by 6-Minute Walk Test, hand grip strength and proximal muscle mass by hand dynamometer, respiratory muscle strength by the Maximum Expiratory Pressure and Maximum Inspiratory Pressure measurements, physical activity by International Physical Activity Questionnaire Short Form, fatigue by Brief Fatigue Inventory, and quality of life by EORT-QLQ-C30. The relationship between functional capacity and continuous independent variables was determined using Spearman's or Pearson's tests. RESULTS: A strong positive correlation was observed between exercise capacity and expiratory muscle strength (r = 0.75, p < 0.001), activity level (r = 0.68, p < 0.001), and quality of life global health status (r = 0.74, p < 0.001). Conversely, a strong negative correlation was found between exercise capacity and fatigue severity (r = -0.64, p < 0.001). CONCLUSION: Higher exercise capacity in cancer cachexia patients is linked to reduced fatigue, improved respiratory muscle strength, increased physical activity levels, and enhanced quality of life. When designing rehabilitation programs or exercise interventions for individuals with cancer cachexia, it is crucial to assess their exercise capacity and tailor the programs accordingly.

The prognostic indicator in breast cancer treated with CDK4/6 inhibitors: the prognostic nutritional index.

Aims: The aim of this study was to evaluate the effect of prognostic nutritional index (PNI) on prognosis in patients with hormone receptor-positive, HER2-negative metastatic breast cancer who received CDK4/6 inhibitor + endocrine therapy. Methods: Patients receiving a CDK4/6 inhibitor were evaluated retrospectively. The PNI was calculated as: (10 × serum albumin [g/dl]) + (total lymphocyte count [×109/l] × 5). Results: In a study of 106 patients, a statistically significant survival advantage was observed in the high-PNI group over the low-PNI group (mean overall survival: 28.03 ± 0.487 months vs 22.46 ± 1.14 months; p = 0.013). Conclusion: For the first time in the literature, this study demonstrated the prognostic role of PNI in patients with hormone receptor-positive, HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors.

Predictors of the 6-min walk test in patients with ovarian cancer.

PURPOSE: To identify the predictors of the 6-min walk test (6MWT) and investigate the relationship between 6MWT, performance status, functional mobility, fatigue, quality of life, neuropathy, physical activity level, and peripheral muscle strength in patients with ovarian cancer (OC). METHODS: Twenty-four patients diagnosed with stage II-III ovarian cancer were included in the study. Patients were assessed using the following measurement methods: 6MWT for walking capacity, Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) for performance status, an armband physical activity monitor for physical activity level, Checklist Individual Strength (CIS) for fatigue, Functional Cancer Treatment Evaluation with Quality of Life-Extreme (FACT-O) for quality of life, Functional Evaluation of Cancer Treatment/Gynecological Oncology-Neurotoxicity (FACT/GOG-NTX) for neuropathy, a hand-held dynamometer for peripheral muscle strength, and 30-s chair-stand test for functional mobility. RESULTS: The mean 6MWT distance was 578.48 ± 115.33 meters. 6MWT distance correlated with ECOG-PS score (r = -0.438, p = 0.032), handgrip strength (r = 0.452, p= 0030), METs (r = 0.414, p = 0.044) 30s-CST (r= 0.417, p= 0.043), and neuropathy score (r = 0.417, p = 0.043) significantly. There was no relationship between 6MWT distance and other parameters (p> 0.05). Multiple linear regression analysis demonstrated that performance status was the sole predictor of 6MWT. CONCLUSION: The walking capacity seems to be associated with performance status, peripheral muscle strength, level of physical activity, functional mobility, and severity of neuropathy in patients with ovarian cancer. Evaluating these may help clinicians to understand factors behind the decreased walking capacity.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

A cross-sectional optical coherence tomography study in patients on taxane-based therapy and a case report with the literature review.

PURPOSE: To evaluate the characteristics of macular retinal and subfoveal choroidal changes in patients already on taxane-based therapy by the help of spectral domain optical coherence tomograpy (SD-OCT) and determine the incidence of taxane- related cystoid macular edema (CME). MATERIALS AND METHODS: In this cross-sectional case-control study, 202 patients who received taxane-based therapy due to treatment of various cancer and age and sex-matched 200 healthy control subjects were examined. Only patients who received at least 4 cycles of taxane-based therapy were taken into consideration for the taxane group. Taxane-based therapy was further divided into two subgroups; paclitaxel group (149 patients) and docetaxel group (53 patients). Central macular thickness (CMT) and central subfoveal choroidal thickness (CCT) were measured just once during their ongoing chemotherapy using SD-OCT and enhanced-depth imaging (EDI) OCT by Heidelberg OCT by a single examiner. RESULTS: Patients received a median of 7 cycles (range, 4-26) of paclitaxel or docetaxel and received a total cumulative dose of 852.81 ± 368.82 mg/m2 (range, 300-2310 mg/m2). Though the mean CMT was significantly thicker in the taxane group (224.9 ± 28.4 µm) than the healthy control group (215.9 ± 19.7 µm), there was no statistically significant difference between the paclitaxel (225.3 ± 28.2 µm) and docetaxel (224.2 ± 20.1 µm) groups. On the other hand, the CCT was not statistically significant different between the taxane versus control eyes and paclitaxel versus docetaxel patients. Taxane-related CME was detected only in one patient on paclitaxel. Overall, incidence of taxane-related maculopathy was 0.5% (1/202) of all patients in the taxane group. CONCLUSION: In our group of taxane receiving patients, incidence of taxane-related CME was 0.5%. In light of our study, we believe that clinicians should be alert on the occurence of taxane-related CME and carefully scrutinize the patients whenever any suspicion is arisen.

An Evaluation of the Information Sources of Cancer Patients' Relatives. A Prospective Survey.

Patients followed up with a cancer diagnosis must be well-informed about cancer to be able to cope with it. Besides, informing the relatives of the cancer patients who are also experiencing the same process about the diagnosis and follow-up period of cancer is highly important. In the current study, it was aimed to evaluate the information sources about cancer which are referred to by relatives of cancer patients. Three hundred ninety-one cancer patient relatives were included in medical oncology clinic between May 1 and June 30, 2015. A questionnaire was applied to the participants, comprising 12 questions to elicit demographic information and 11 questions about the information sources to which they referred. The study included 183 female and 208 male participants with a mean age of 47.9 ± 13.6 years. While the oncologists were the primary information sources referred to by 87%, the Internet was the second most preferred information source by 72%. The websites most frequently referred were the official websites (70%), the websites of oncology associations (53%), and social networks and forums (32%). The primary factors affecting the Internet preference were age, education level, income level, and place of residence. The Internet was the second most referred information source about cancer by family caregivers following oncologists. Therefore, it is of crucial importance that physicians inform patients and their relatives comprehensively as well as guiding them to correct and reliable information sources.

Tumor deposits in salivary gland tumors.

Tumor deposits (TDs), identified in different types of carcinomas are associated with poor prognosis. Salivary gland tumors were evaluated for the first time for TDs in this series. Pathological and clinical features of 25 salivary gland carcinomas primarily treated surgically including neck dissection were determined and all cases were evaluated for TDs in dissection specimens. Seven patients (28%) had TDs. There was no difference for TDs when histological type, tumor grade, tumor localization, pT, pN stage, surgical margin, lymphovascular, perineural invasion, local recurrence, distant metastatic disease and overall survival were considered. Disease-free survival rates at 12 and 24 months were 52.5%, 28.6% and 73.3%, 57.1%, for cases with and without TDs (P = 0.463). Overall survival rates at 12 and 24 months for these groups were 85.7% and 57.1 versus 86.7% and 66.7% respectively (P = 0.916). Mean estimated recurrence-free survival time for all cases, TD negative and TD positive cases were: 171.86, 182.72 and 82.42 months, respectively. Mean estimated overall survival time for these groups were 175.80, 186.489 and 89.70 months, respectively. TDs were described in salivary gland tumors for the first time in this series and seem to be associated with poor prognosis requiring further evaluation in larger series.

Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Patients with Neuroendocrine Tumors: An Izmir Oncology Group Study.

BACKGROUND: Several studies evaluating the prognostic factors of gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs) have been published. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been accepted as prognostic factors for cancer patients. MATERIALS AND METHODS: This study included 132 patients diagnosed with GEP-NETs. Peripheral blood samples were collected before the pretreatment period. RESULTS: NLR and PLR were increased as the grade increased in NETs. The embryonic origin analysis revealed higher NLR and PLR rates in NETs of foregut origin. NLR and PLR were also higher in pancreatic NET patients compared to the gastroenteric NET patients. Analysis of NETs by TNM indicated that an advanced stage was accompanied by significantly higher NLR and PLR. We found a strong negative correlation between progression-free survival and NLR and PLR. CONCLUSION: The study verified that NLR and PLR are simple laboratory findings that can be used to identify NETs with a worse outcome.

Dihydropyrimidine dehydrogenase 85T>C mutation is associated with ocular toxicity of 5-fluorouracil: a case report.

5-Fluorouracil (5-FU), the mainstay of solid tumor chemotherapy over the past 40 years, induces grade III-IV toxicities in up to 15% of patients with polymorphisms in the dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR) genes. These toxicities include mucositis, neutropenia, nausea, diarrhea, myelosuppression, hand-foot syndrome, and rare ocular adverse effects. Here, we present the case of a female patient with rectal cancer who received 5-FU-based chemotherapy and developed grade III hand-foot syndrome and rare acute ocular adverse effects. Genetic analysis revealed that the patient had an 85T>C mutation in the DPYD gene resulting in a DPYD*9A allele. The clinical and molecular observations indicate that DPYD deficiency may be responsible for the severe ocular adverse effects observed in 5-FU-treated patients. Application of personalized therapy based on molecular testing should help clinicians provide the most effective chemotherapy agents and dose modifications for each patient, although further population-based pharmacogenetic trials for the 5-FU metabolism-related genes are necessary to minimize adverse effects and enhance clinical outcomes.

Cutaneous melanoma in Turkey: analysis of 1157 patients in the Melanoma Turkish Study.

PURPOSE: To develop a large Turkish National Melanoma registry in order to define demographic and clinicopathologic characteristics of patients with melanoma. METHODS: The data was collected from 1635 patients with melanoma through a web-based registry system in 22 centers. Herein we present the results of 1157 patients with cutaneous melanoma. RESULTS: The patient median age was 56.4 years and 646 (55.8%) were males. The commonest subtype was superficial spreading type (357, 30.9%). The commonest primary site was the lower extremities (N=353, 30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only 104 (12.5%) patients had a thickness <1mm. Among 694 patients with available data, 136 (19.6%) presented with stage 4 disease while the most frequent stage was stage 3, encountered in 393 (56.6% patients). CONCLUSION: Our melanoma registry is the largest in our country providing a snapshot view of cutaneous melanoma and its care. Our patients presented with more advanced stages and they had worse prognosis compared to SEER database.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

Long-term outcomes and prognostic factors of high-risk malignant melanoma patients after surgery and adjuvant high-dose interferon treatment: a single-center experience.

BACKGROUND: Surgical excision constitutes an important part of the treatment of local advanced malignant melanoma. Due to the high recurrence risk, adjuvant high-dose interferon therapy is still the only therapy used in stage IIB and III high-risk melanoma patients. METHODS: One hundred two high-risk malignant melanoma patients who received high-dose interferon-α-2b therapy were evaluated retrospectively. The clinicopathological features, survival times, and prognostic factors of the patients were determined. RESULTS: The median disease-free and overall survival times were 25.2 and 60.8 months, respectively. Our findings revealed that male gender, advanced disease stage, lymph node involvement, lymphatic invasion, the presence of ulceration, and a high Clark level were significant negative prognostic factors. CONCLUSION: In light of the favorable survival results obtained in this study, high-dose interferon treatment as adjuvant therapy for high-risk melanoma is still an efficient treatment and its possible side effects can be prevented by taking the necessary precautions.

Neutrophil-to-lymphocyte ratio: could it be used in the clinic as prognostic marker for gastrointestinal stromal tumor?

BACKGROUND/AIMS: The association between systemic inflammatory response and tumor biology has been well documented over the last decade. The aim of this study is to investigate the prognostic role of neutrophilto- lymphocyte ratio (NLR) in gastrointestinal stromal tumors (GISTs). METHODOLOGY: A prospectively recorded database of 67 patients who underwent surgical resection for GIST was reviewed. High and low NLR were defined with respect to the sample median, which was 1.92. Demographical, clinicopathological, and surgical characteristics were analyzed as well as disease free survival (DFS) rates according to NLR classification. RESULTS: We observed better disease free survival rates in patients with low NLR compared to patients with high NLR (85.7% and 69%, respectively; p=0.037). Estimated five-year overall and disease free survival rates were 95.1% and 78.7%, respectively. In univariate analysis synchronous sarcomatosis, tumor size, mitotic rate, presence of necrosis, lymph node metastasis, surgical margin status, risk category and NLR were associated with DFS. On multivariate analysis sarcomatosis (HR: 30.455), surgical margin status (HR: 4.228) and necrosis (HR: 4.415) were found as independent prognostic factors for DFS. CONCLUSIONS: NLR can give information about inflammatory status, tumor aggressivity and prognosis in GIST patients. It could be a new prognostic factor for GIST patients.

Is the percentage of hormone receptor positivity in HR+ HER2-metastatic breast cancer patients receiving CDK 4/6 inhibitor with endocrine therapy predictive and prognostic?

Purpose: There is no clear information in the literature about the relationship between the efficacy of CDK 4/6i combined with ET and HR positivity. However, we know that the longest overall survival was in the ER-strong positive/PR intermediate or strong positive groups. Therefore, we aimed to investigate CDK4/6i treatments that create positivity in HR. Methods: Patients with the diagnosis of HR+/HER2- MBC who were treated with CDK 4/6i and HR >10% were retrospectively evaluated. To analyze the role of HR positivity, ER was moderately positive (10-49%) and ER was strongly positive (50-100%); PR was grouped as moderately positive (10-49%) and PR strongly positive (50-100%). Results: Median follow-up of 150 patients included in the study was 15.2 months (95% CI, 2.1-40.9 months). The highest response in the whole group was obtained in the ER-strong positive/PR moderate or strong positive group, and the ER moderate positive/PR moderate or strong group. This was followed by the ER strong positive/PR negative group, and then the ER moderate positive/PR negative group. Although these advantages were not statistically significant, they were numerically higher (ORR: 83.8% vs. 83.3% vs. 77.4% vs. 62.5%, p=0.488, respectively). The highest survival in the whole group was achieved in the ER strong positive/PR moderate or strongly positive group, followed by the ER moderately positive/PR moderate or strongly positive group, the ER strongly positive/PR negative group followed by the ER moderate positive/PR negative group, respectively(p=0.410). However, these advantages were not statistically significant. Conclusion: As a result, HR+/HER2- MBC patients receiving CDK 4/6i combined with ET suggest that the percentage of HR positivity may have a predictive and prognostic role.

lncRNA XIST Interacts with Regulatory T Cells within the Tumor Microenvironment in Chronic Hepatitis B-Associated Hepatocellular Carcinoma.

OBJECTIVE: Alterations in the expression of several long non-coding RNAs (lncRNAs) have been shown in chronic hepatitis B-associated hepatocellular carcinoma (CHB-HCC). Here, we aimed to investigate the association between the expression of inflammation-associated lncRNA X-inactive specific transcript (XIST) and the type of inflammatory cells within the tumor microenvironment. MATERIAL AND METHODS: Twenty-one consecutive cirrhotic patients with CHB-HCC were included. XIST expression levels were investigated on formalin-fixed paraffin-embedded (FFPE) tumoral and peritumoral tissue samples by real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining for CD3, CD4, CD8, CD25, CD163, CTLA4, and PD-1 were performed. The findings were statistically analyzed. RESULTS: Of the 21 cases, 11 (52.4%) had tumoral and 10 (47.6%) had peritumoral XIST expression. No significant association was found between the degree of inflammation and XIST expression. The number of intratumoral CD3, CD4, CD8 and CD20 positive cells was higher in XIST-expressing tumors, albeit without statistical significance. Tumoral and peritumoral XIST expression tended to be more common in patients with tumoral and peritumoral CD4high inflammation. The number of intratumoral CD25 positive cells was significantly higher in XIST-expressing tumors (p=0.01). Tumoral XIST expression was significantly more common in intratumoral CD25high cases (p=0.04). Peritumoral XIST expression was also more common among patients with CD25high peritumoral inflammation, albeit without statistical significance (p=0.19). CONCLUSION: lncRNA XIST is expressed in CHB-HCC and its expression is significantly associated with the inflammatory tumor microenvironment, particularly with the presence and number of CD25 (+) regulatory T cells. In vitro studies are needed to explore the detailed mechanism.

The prognostic significance of PD-1 and its ligands in non-small cell lung cancer.

Background: In this study, we aimed to investigate the prognostic value of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and programmed cell death ligand 2 (PD-L2) expressions on immune and cancer cells in terms of survival in patients with lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Methods: Between January 2000 and December 2012, a total of 191 patients (172 males, 19 females; mean age: 60.3±8.4 years; range, 38 to 78 years) who were diagnosed with non-small cell lung cancer and underwent anatomic resection and mediastinal lymph node dissection were retrospectively analyzed. The patients were evaluated in three groups including lung squamous cell carcinoma (n=61), adenocarcinoma (n=66), and large-cell carcinoma (n=64). The survival rates of all three groups were compared in terms of immunohistochemical expression levels of PD-1, PD-L1, and PD-L2. Results: The mean follow-up was 71.8±47.9 months. In all histological subtypes, PD-1 expressions on tumor and immune cells were observed in 33% (61/191) and in 53.1% (102/191) of the patients, respectively. Higher expression levels of PD-L1 and PD-L2 at any intensity on tumor and immune cells were defined only in lung adenocarcinomas, and PD-L1 and PD-L2 values were detected in 36.4% (22/64) of these patients. The PD-L1 expressions on tumor and immune cells were observed in 41.7% (10/24) and 25% (6/24) of the patients, respectively. The PD-L2 expressions on tumor and immune cells were detected in 16.7% (4/24) and 8.4% (2/24) of the patients, respectively. Univariate and multivariate analyses revealed that PD-1 expression in tumor cells was an independent prognostic factor in all histological subtypes. Conclusion: Our study results suggest that PD-1 expression is a poor prognostic factor for overall survival in patients with completely resected adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

Complications and toxicities after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: The purpose of our study was to evaluate the perioperative complications, toxicity, mortality rates after cytoreductive surgery (CRS), and effects of hyperthermic intraperitoneal chemotherapy (HIPEC) used in the treatment of peritoneal surface malignancies. METHODS: Between September 2007 and March 2012, we performed 118 CRS and HIPEC with the closed abdominal technique on 115 patients with peritoneal carcinomatosis (PC). Systemic toxicities were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria and were analyzed from a prospectively collected database. RESULTS: The mean age of patients was 53.4 (range, 20-82) years; 76.3 % were female. PC was synchronous to primary cancer in 53.4 % of patients, metachronous in 41.5 %, and recurrent in 5.1 % of the patients. PCI was ≥15 in 53.4 % of the patients, and CC-0 cytoreduction was achieved in 68.5 % of the patients. Perioperative mortality was observed in 9 (7.6 %) patients. A total of 98 complications were observed in 46 (39.0 %) patients, and 4 patients underwent 6 reoperations for perioperative surgical complications. We observed toxicity in 25.4 % of the patients, nephrotoxicity in 18.6 %, and hematological toxicity in 13.6 % of patients. No significant difference was observed among age, gender, PCI and CC scores, origin of the primary tumor, and occurrence of toxicity and surgical complications. Prolonged operation times resulted in higher complication and/or toxicity rates (P < 0.01). CONCLUSIONS: Cytoreductive surgery and HIPEC is a combined treatment strategy for peritoneal surface malignancies with acceptable complication and toxicity rates.

Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected liver metastases from colorectal cancer.

BACKGROUND: We aimed to investigate the impact of adjuvant systemic therapy with modern chemotherapy combinations on survival outcomes in patients with resected liver-confined metastases from colorectal carcinomas, and whether addition of bevacizumab (BEV) provides further benefit. METHODS: A total of 229 consecutive patients who underwent resection for liver-confined colorectal liver metastases were retrospectively analyzed. RESULTS: Of 229 patients, 204 who received chemotherapy with fluoropyrimidine-based (n = 27), irinotecan-based (n = 84) and oxaliplatin-based (n = 93) combinations were analyzed. Among these, 87 patients received BEV while 117 did not (NoBEV). With a median follow-up of 27 months after metastasectomy, the median recurrence-free survival (RFS) and overall survival (OS) were 17 and 53 months, respectively. OS rates at 3 and 5 years were 71% and 40%, respectively. No significant differences were found in the median RFS (p = 0.744) and OS (p = 0.440) among different chemotherapy regimens. The median RFS (p = 0.375) and OS (p = 0.251) were similar in BEV and NoBEV arms. In multivariate analysis, having 4 liver metastases was the only negative independent factor on both RFS and OS, while positive surgical margin was another negative independent factor for RFS. CONCLUSION: Chemotherapy type and addition of BEV have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal liver metastases.

Bimonthly regimen of high-dose leucovorin, infusional 5-fluorouracil, docetaxel, and cisplatin (modified DCF) in advanced gastric adenocarcinoma.

BACKGROUND: The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) is an effective but highly toxic regimen for the treatment of advanced gastric cancer. To improve tolerability while maintaining the efficacy of the DCF regimen, we developed a modified DCF regimen including an infusional 5-fluorouracil administration according to the de Gramont regimen. METHODS: In this study, 70 patients with advanced gastric cancer were treated. Each 2-week cycle consisted of docetaxel (60 mg/m(2)), cisplatin (50 mg/m(2)), a 5-fluorouracil (400 mg/m(2)) i.v. bolus, and 5-fluorouracil (2,400 mg/m(2)) i.v. over 46 h plus leucovorin (400 mg/m(2)) i.v. over 2 h. RESULTS: The median progression-free survival and overall survival were 9.0 months (95% CI, 7.1-10.9) and 10.8 months (95% CI, 7.4-14.2), respectively; the 1-year and 2-year overall survival rates were 46.3 and 18.4%, respectively. Twenty-nine (41.4%) partial responses, 19 (27.1%) stable disease, and 22 (31.4%) progression of disease were observed. Grade 3-4 toxicities included neutropenia (37.1%), febrile neutropenia (15.7%), thrombocytopenia (10.0%), anemia (8.6%), nausea and vomiting (10.0%), stomatitis (5.7%), infection (8.6%), and diarrhea (2.9%). CONCLUSIONS: Our results show that a de Gramont-based DCF regimen may have tolerable toxicities and be an effective and convenient palliative treatment for advanced gastric cancer.

CD40 expression in pancreatic cancer.

BACKGROUND: CD40, a tumor necrosis factor receptor family member, is expressed in a variety of cell types. This widespread expression suggests that CD40 may play an important role in normal physiology and disease pathogenesis. The objective of the current study was to investigate the expression of CD40, and its association with clinicopathological features and survival in patients with pancreatic ductal adenocarcinoma. METHODOLOGY: CD40 expression was assessed in 53 pancreatic ductal adenocarcinoma surgical specimens by immunohistochemistry, and expression was correlated with patient clinicopathological parameters and outcome. RESULTS: Among 53 pancreatic cancer specimens, CD40 expression was detected in 13 specimens (24.5%), and peritumoral lymphocytes were present in 45 specimens (84.9%). Patients with CD40-positive tumors exhibited prolonged median disease-free survival (DFS) compared with patients with CD40-negative tumors (15.60 +/- 3.87 versus 10.03 +/- 1.92); however, this was not significant (p = 0.845). Patients with peritumoral lymphocytic reaction exhibited prolonged median DFS compared with patients without peritumoral lymphocytes (10.96 +/- 1.40 vs. 7.60 +/- 0.47); however, this was not significant (p = 0.624). Patients with peritumoral lymphocytic reaction exhibited higher median overall survival compared with patients without peritumoral lymphocytes (15.20 +/- 1.78 vs. 10.13 +/- 1.39); however, again this was not significant (p = 0.100). CONCLUSIONS: These results suggest that CD40 expression on pancreatic cancer cells and peritumoral lymphocytic reaction may serve as prognostic markers.