Small bowel wall edema induced by regorafenib is associated with regorafenib intolerance and shorter survival in patients with metastatic colorectal cancer: A retrospective study.

INTRODUCTION: Regorafenib, a receptor tyrosine kinase inhibitor, is a routinely used targeted agent in the current treatment of patients with refractory metastatic colorectal carcinoma (mCRC). The aims of this study were to detect the presence of bowel wall edema during regorafenib treatment via computed tomography (CT) and to assess the relationship between survival and regorafenib-induced bowel wall edema in patients with mCRC receiving regorafenib. PATIENTS AND METHODS: We retrospectively evaluated the presence of bowel wall edema on CT of 25 mCRC patients who received regorafenib and analyzed its relationship with progression free survival (PFS) and overall survival (OS). RESULTS: Among the 25 patients, 25 had small bowel wall edema (SBWE) and 14 had large bowel wall edema (LBWE) on at least one CT examination. The median SBWE value was 4.85 milimeters (mm). Of the 25 patients, 14 had SBWE ≤4.85 mm and 11 had SBWE >4.85 mm. Regorafenib intolerance was significantly higher at SBWE >4.85 mm patients (p = 0.03). The median PFS was 4.6 months (95% CI: 2.4-6.8) and median OS was 9.3 months (95% CI: 3.1-15.4). Median PFS and OS were shorter in patients with SBWE > 4.85 mm than in those with ≤4.85 mm, but not statistically significant (median PFS: 3.9 vs 4.6 months, p: 0.523; median OS: 5.6 vs 9.3 months, p: 0.977). CONCLUSIONS: Regorafenib caused SBWE in patients with mCRC. Patients who developed more SBWE had a higher regorafenib intolerance and a shorter survival. Further studies are needed to confirm the predictor value of SBWE on the survival outcomes of patients with mCRC receiving regorafenib.

Severe periocular bleeding induced by bevacizumab in a patient with recurrent glioblastoma multiforme.

Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor, and it has been shown to improve progression-free survival in patients with recurrent glioblastome multiforme when administered as second-line therapy. However, it has been associated with serious and fatal hemorrhagic events. Here, we present a 68-year-old male who developed severe periocular bleeding while on bevacizumab for recurrent temozolamide-resistant glioblastome multiforme.

Fatal posterior revesible leukoencephalopathy syndrome associated coma induced by bevacizumab in metastatic colorectal cancer and review of literature.

Posterior reversible leukoencephalopathy syndrome (PRES) is a syndrome characterized by headache, hypertension, confusion, visual disturbance, and seizures accompanied by subcortical vasogenic edema, predominantly involving the parietal and occipital lobes. The syndrome is usually described in malignant hypertension, eclampsia, renal failure, immunosuppressive, and cytotoxic chemotherapies. Bevacizumab, a monoclonal antibody that binds to the vascular endothelial growth factor (VEGF) has been linked to PRES. We carried out review of reports documenting the occurrence of PRES in patients receiving bevacizumab. This literature review was conducted by utilizing PubMed Database. If early diagnosed, PRES is reversible. We present a case of fatal PRES-associated coma induced by bevacizumab in metastatic colorectal cancer.

Ipilimumab may increase the severity of cutenaous toxicity related to radiotherapy.

Ipilimumab, monoclonal antibody against cytotoxic T-lymphocyte antigen-4 and, radiotherapy are commonly used to treat unresectable and metastatic melanoma. As a result of upregulation of immune system with ipilimumab, many immune-related adverse effects, such as dermatitis, colitis, hepatitis, and hypophysitis, have been previously reported in literature. Typically, these effects are treated with high-dose steroids and mostly heal up. Here, we report a case who was receiving radiotherapy due to metastatic malignant melanoma with atypical generalized rash, which was enlarged with concurrent ipilimumab treatment.

Sorafenib-induced severe urticaria in a patient with hepatocellular cancer.

Sorafenib which is used in the treatment of renal, thyroid and hepatocellular cancers is a multi-targeted tyrosine kinase inhibitor. Though sorafenib is associated with some side effects, it is known that sorafenib is generally well tolerated compared to other tyrosine kinase inhibitors. In the present case, hepatocellular cancer was diagnosed seven months ago. The disease was in stage IIIB at the time of diagnosis. Sorafenib was initiated with a dose of 400 mg twice daily because of disease progression after two cycles of doxorubicin. The reactions on the skin of the arms and the body of the patient occurred in the eighth week of treatment. Skin biopsy was performed and urticaria was diagnosed after pathologic examination. No other disorders or drugs which may cause urticaria were detected in the patient. Skin reactions disappeared one week after sorafenib discontinuation without any further intervention.

Metronomic maintenance chemotherapy in patients presenting with paraneoplastic autoimmune hepatitis with recurrent thymic carcinoma.

Autoimmune hepatitis is a rarely seen autoimmune paraneoplastic syndrome of thymic carcinoma. Chemotherapy may be an effective choice in the treatment of primary tumor and paraneoplastic disorder. In this case, we report a 32-year-old man presented with increased liver enzymes and cholestasis with a history of thymoma surgically removed four years ago. Liver biopsy showed chronic active autoimmune hepatitis. Computed tomography scan showed pulmonary metastases and pleural mass as a recurrence of thymic carcinoma, proven by biopsy. After four cycles of cisplatin plus adriamycin plus cyclophosphamide plus vincristine and six cycles of paclitaxel plus gemcitabine, maintenance metronomic cyclophosphamide plus etoposide regimen was offered to the patient. Complete biological signs of hepatitis without need for steroids or immune suppressors and complete radiologic response in primary tumor were achieved. Maintenance metronomic chemotherapy regimens may be an alternative to the current treatment options in patients with thymic carcinomas.

Is there any relation between PET-CT SUVmax value and prognostic factors in locally advanced breast cancer?

PURPOSE: To investigate the relation between PET-CT SUVmax value and prognostic factors in locally advanced breast cancer. METHODS: Data of 73 patients were retrospectively analyzed. Relations between SUVmax value, clinical stage, tumor grade and breast cancer molecular subtypes were analyzed by using one-way ANOVA and x(2) tests. Correlations between age, ki-67 scores and SUVmax were evaluated by using Pearson's correlation test. A p value <0.05 was considered statistically significant. RESULTS: Median SUVmax values for clinical stages 1, 2 and 3 were 5 (range 2.1-4.1), 10.6 (range 2.9-19.6), and 12.2 (range 3.2-23.3), respectively. Statistically significant difference was noticed between stage 1 and 2 (p=0.014) and stage 1 and 3 (p=0.001). Median SUVmax values of triple negative, luminal A, luminal B and non-luminal HER2 positive groups were 14.4 (range 6.6-23.3), 8.2 (range 2.1-18.2), 10.1 (range 3.5-19.6), and 14 (range 4.1-22.9), respectively. Statistically significant differences were noticed in SUVmax values between triple-negative and luminal A groups (p=0.005) and between non-luminal HER2 positive and luminal A groups (p=0.02). Median SUVmax values of grade 1, 2 and 3 were 5.7 (range 2.1-18.2), 9.5 (range 2.2-21.3), and 11.6 (range 3.5-23), respectively. Statistically significant difference was noticed only between SUVmax values of grade 1 and 3 (p=0.035). There was negative correlation between age and SUVmax value (r=-0.23, p=0.047) and positive correlation between ki-67 and SUVmax value (r=0.43, p=0.016). CONCLUSION: There were significant positive relations between PET-CT SUVmax value and clinical stage, tumor grade, and certain breast cancer molecular subtypes (triple-negative and non-luminal HER2 positive groups. Moreover, positive correlation was found between SUVmax value and ki-67 and negative correlation between SUVmax value and age.

Hemangiopericytoma of the skull base: A long-term complete response with trimodality treatment.

Hemangiopericytoma (HPC) is a rare tumor originating from Zimmerman pericytes. It constitutes less than 1% of all intracranial tumors. Because of the high recurrence rates, radiotherapy (RT) is a vital step in the treatment, but the timing and dose remain uncertain. We presented a 39-year-old patient with a high-grade hemangiopericytoma located at the skull base. The patient presented with a severe headache. Cranial magnetic resonance imaging (MRI) revealed a mass of size of 60 × 50 mm. A subtotal resection was performed that confirmed the diagnosis of HPC. The patient received 66 Gy postoperative RT. Adjuvant sunitinib treatment was initiated after RT. The complete regression was achieved in the third month after RT. The patient has a complete response for 25 months. To our knowledge, this case is one of the rare cases in the literature in which immediate RT and adjuvant chemotherapy were used in combination with surgery. Although HPC is a radio- and chemo-resistant disease, a trimodality treatment approach can provide the patients with a complete response. In particular, patients with high-grade and inoperable tumors and patients who undergo subtotal resection should be evaluated for trimodal therapy.

Mediastinal small cell carcinoma with a metastasis to the orbit: A rare carcinoma with an unusual metastatic progression.

Extraocular muscle (EOM) is a rare site for orbital metastasis. We presented a case of solitary EOM metastasis from mediastinal small cell cancer (MSCC) for the first time. A 49-year-old man presented with hoarseness. Thorax computed tomography (CT) revealed a mediastinal mass. A fine-needle aspiration biopsy (FNAB) confirmed the diagnosis of MSCC. The patient staged as limited-stage MSCC with a positron emission computed tomography (PET-CT). The patient received radical chemo-radiotherapy (CRT). PET-CT showed a complete response after CRT. Afterward, the patient presented with double vision and a headache. Brain magnetic resonance imaging (MRI) demonstrated a 2 cm metastatic lesion at the left inferior rectus muscle. A 30 Gy palliative RT was applied. The full regression of the mass was achieved 3 months after the palliative RT. Although solitary EOM metastasis is rare, the timing of accurate diagnosis and appropriate treatment can help to preserve the patient's vision and relieve complaints related to the mass.

Hypercalcemia associated with squamous cell carcinoma of renal pelvis: A case and review of the literature.

Renal pelvis squamous cell carcinoma (RSCC) is a rare tumor. It starts with nonspecific symptoms and it is usually at an advanced stage with a poor prognosis at the time of diagnosis. SCC-associated hypercalcemia is a well-known paraneoplastic syndrome; however RSCC-associated hypercalcemia is a rare condition. Our patient is a 57-year-old-male patient with no bone metastases. Based on the literature screening on PubMed Database for paraneoplastic malignant hypercalcemia-associated RSCC, we found a few cases.

The importance of stromal and intratumoral tumor lymphocyte infiltration for pathologic complete response in patients with locally advanced breast cancer.

OBJECTIVE: Increased tumor-infiltrating lymphocytes (TILs) in breast carcinoma tissues is an independent predictive factor for pathologic complete response (pCR). The increased intratumoral and stromal TILs (sTILs) in breast cancer (BC) have significant prognostic effects. In this study, we evaluated whether pCR rates to neoadjuvant chemotherapy (NACT) are higher in tumors with increased number of TILs in the pretreatment biopsy. MATERIALS AND METHODS: We retrospectively evaluated the number of TILs in intratumoral TILs (iTILs) and sTILs compartments from pretreatment full-face hematoxylin and eosin-stained sections of 62 patients with locally advanced BC (LABC) who received NACT. The capacity of sTILs and iTILs in predicting pCR to NACT in LABC analyzed using receiver operating characteristic (ROC) curve analysis. RESULTS: According to ROC curve analysis, the optimum sTILs and iTILs cut-off points (the number of positive cells per square millimeter of tissue) for patients with LABC patients with pCR (+) were 19 (area under the curve (AUC): 0.668, 95% confidence interval [CI] [0.501-0.835],P = 0.064) and 4 (AUC: 0.786, 95%CI [0.666-0.907],P = 0.002), respectively. Of the 62 patients, 26 had sTILs >19 and 25 had iTILs >4. The patients were divided into two according to percent of sTILs (sTILs >19 and sTILs ≤19 groups) and iTILs (iTILs >4 and iTILs ≤4 groups). Both sTILs >19 and iTILs >4 patients were associated with development higher pCR. While pCR was significantly higher in iTILs >4 patients (P = 0.002), it was not significantly in sTILs >19 patients (P = 0.107). CONCLUSIONS: There is significantly an association between pCR and increased number of intratumoral TILs (>4 cells/mm 2 of tissue) in BC who received NACT.

Docetaxel plus cisplatin plus fluorouracil versus carboplatin plus fluorouracil-cetuximab in first-line setting in patients with recurrent or metastatic head and neck squamous cell cancer who did not previously receive neoadjuvant or adjuvant chemotherapy, which is standard?

BACKGROUND: The prognosis of recurrent or metastatic head and neck squamous cell cancer (HNSCC) is very poor. In the present retrospective study, we compared the impact of docetaxel plus cisplatin plus fluorouracil (TCF), and cisplatin plus fluorouracil plus cetuximab (CF-Ctx) regimens on the prognosis of patients with recurrent or metastatic HNSCC in first-line. MATERIALS AND METHODS: A total of 70 patients were evaluated as two groups, according to treatment protocol: TCF (n: 47) and CF-Ctx (n: 23). The groups were compared regarding survival. RESULTS: The median progression-free survival was 7.3 and 8.3 months, TCF and CF-Ctx groups, respectively, (P = 0.280). The median overall survival (OS) was 15.6 and 9.3 months for TCF and CF-Ctx groups, respectively, (P = 0.029). The dose reduction and using of granulocyte colony stimulating factor were significantly higher in TCF group (P = 0.048 and P = 0.018, respectively). CONCLUSION: In first-line setting, TCF regimen is superior to CF-Ctx regimen in terms of OS in patients with recurrent or metastatic HNSCC, who did not previously receive neoadjuvant or adjuvant chemotherapy.

Multiple pelvic cysts in a patient with familial Mediterranean fever: Benign cystic mesothelioma.

Benign cystic mesothelioma (BCM) is a rare tumor arising from endothelial cells of the pelvic visceral or parietal peritoneum. It is a clinically and histopathologically benign disease. Etiology and pathogenesis of BCM remain unclear. Familial Mediterranean fever (FMF) is an inherited disorder characterized by episodes of fever, and abdominal, chest and/or joint inflammation. Association between malignant mesothelioma and FMF has been reported previously; however, co-existence of FMF and BCM is rare. Here, we report a case of BCM in a 43-year-old male patient with FMF.

Primary Tumor Resection and Survival in Patients with Stage IV Gastric Cancer.

PURPOSE: The aim of this study was to determine whether surgical resection of the primary tumor contributes to survival in patients with metastatic gastric cancer. MATERIALS AND METHODS: A total of 288 patients with metastatic gastric cancer from the Akdeniz University, Antalya Training and Research Hospital, and the Meram University of Konya database were retrospectively analyzed. The effect of primary tumor resection on survival of patients with metastatic gastric cancer was investigated using the log-rank test. Kaplan-Meier survival estimates were calculated. Multivariate analysis was performed using Cox proportional hazards regression modeling. RESULTS: The median overall survival was 12.0 months (95% confidence intewrval [CI], 10.4~13.6 months) and 7.8 months (95% CI, 5.5~10.0 months) for patients with and without primary tumor resection, respectively (P<0.001). The median progression-free survival was 8.3 months (95% CI, 7.1~9.5 months) and 6.2 months (95% CI, 5.8~6.7 months) for patients with and without primary tumor resection, respectively (P=0.002). CONCLUSIONS: Non-curative gastrectomy in patients with metastatic gastric cancer might increase their survival rate regardless of the occurrence of life-threatening tumor-related complications.

The Neutrophil to Lymphocyte Ratio is an Independent Prognostic Factor in Patients with Metastatic Gastric Cancer.

Inflammation can play an important role in cancer progression and the prognostic importance of neutrophil to lymphocyte ratio (NLR), a marker of inflammation, in cancer is a current investigation topic. In the present study, we aimed to determine whether there is a prognostic link between NLR and metastatic gastric cancer (mGC). A total of 143 patients from the Akdeniz University and Antalya Training and Research Hospital database were retrospectively analyzed. The median NLR value was 3.34. The median overall survival (OS) and median progression-free survival (PFS) were 11.6 and 7.9 months, respectively, in patients with NLR<3.34 while these values were 8.3 and 6.2 months respectively in patients with NLR >3.34 (p<0.001 and p=0.011, respectively). Our study showed that increased NLR is an independent prognostic factor associated with short survival in patients with mGC.

Mean Platelet Volume as an Independent Predictive Marker for Pathologic Complete Response after Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer.

BACKGROUND: The impact of mean platelet volume (MPV) on prognosis, diagnosis and response to therapy in cancer patients has been widely investigated. In the present study, we evaluated whether MPV at diagnosis has predictive value for pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC). MATERIALS AND METHODS: A total of 109 patients with LABC from Akdeniz University and Antalya Research and Training Hospital were evaluated retrospectively. RESULTS: ROC curve analysis suggested that the optimum MPV cut-off point for LABC patients with pCR (+) was 8.15 (AUC:0.378, 95%CI [0.256- 0.499], p=0.077). The patients with MPV <8.15 had higher pCR rates (29.2% vs. 13.1%, p=0.038). After binary logistic regression analysis, MPV and estrogen receptor absence were independent predictors for pCR. CONCLUSIONS: MPV has an independent predictive value for pCR after neoadjuvant chemotherapy in patients with LABC.

Metronomic oral chemotherapy with old agents in patients with heavily treated metastatic breast cancer.

BACKGROUND: We aimed to assess the efficacy of a metronomic regimen with cyclophosphamide and etoposide in heavily treated patients with metastatic breast cancer (MBC). MATERIALS AND METHODS: A total of 77 patients with MBC used continuous oral cyclophosphamide 50 mg/day and oral etoposide given as 2 × 50 mg/day for 2 days per week, were analyzed retrospectively from Akdeniz University and Selcuk University. The patients with MBC are predominantly refractory to antracyclines, taxanes, and antimetabolites. RESULTS: The patients were treated and followed between May 2005 and June 2014. The median progression-free and overall survival (PFS and OS) were 7.03 (5.06-8.99) and 32.5 (22.5-42.4) months, respectively. No prognostic factor was found for OS. CONCLUSIONS: Metronomic treatment regimen with cyclophosphamide and etoposide is a novel and effective strategy in heavily pretreated MBC patients. This regimen can be used in early or late steps as independently from prognostic factors. Moreover, it has very low toxicity and is cheap. Impressive survival data and low cost may make this regimen a highly preferable option.

Experience of bevacizumab in a patient with colorectal cancer after renal transplantation.

Bevacizumab is a drug that is widely used for the first-line treatment of metastatic colorectal cancer (mCRC). Bevacizumab neutralizes vascular endothelial growth factor and can lead to proteinuria and renal damage. In this case, experience on full dose short-time treatment of bevacizumab in a patient under immunosuppressive treatment for renal transplantation with chronic renal failure has been shared. The patients were diagnosed with mCRC 7 months ago. The patient had multiple liver metastases at the time of the diagnosis. He had a history of renal transplantation 2 years ago because of renal failure, and he had been under immunosuppressive treatment for this reason. 5-fluorouracil-leucovorin-irinotecan -bevacizumab regimen was begun for the treatment of mCRC. The dose of bevacizumab was 5 mg/kg/day for 14 days. There was 2.5 g/day of proteinuria at the start of the treatment. However, renal dysfunction progressed, and proteinuria increased to 4 g/day in the 3rd month of treatment. In this case, the experience of using bevacizumab in a patient under immunosuppressive treatment for renal transplantation with chronic failure has been presented.

Neutrophil to lymphocyte ratio is an independent prognostic factor in patients with recurrent or metastatic head and neck squamous cell cancer.

The neutrophil to lymphocyte ratio (NLR) has been widely investigated for its prognostic significance in cancer. In the present study, we aimed to determine whether NLR is a prognostic factor in patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC). A total of 79 patients from the Akdeniz University database were retrospectively analyzed. The cut-off NLR was set at 2.93; patients with NLR >2.93 had a median overall survival (OS) of 12.1 months, whereas the median OS was not reached for patients with NLR ≤2.93 (P=0.027). On multivariate analysis, NLR and recurrence or metastatic site were found to be independent prognostic factors for OS (P=0.014 and P=0.002, respectively). Therefore, NLR was identified as an independent prognostic factor for OS in patients with recurrent or metastatic HNSCC.