Tyrosine kinase inhibitors in the treatment of metastatic renal cell cancer patients with early cytokine intolerance: TURCOS, a Turkish national, prospective observational study.

OBJECTIVE: Cytokines have been the mainstay of treatment in metastatic renal cell cancer (mRCC) for decades before the introduction of tyrosine kinase inhibitors (TKIs), which dramatically changed the therapeutic landscape in these patients. This observational study was designed to evaluate use of TKIs in the treatment of cytokine-intolerant mRCC patients. METHODS: A total of 151 cytokine-intolerant mRCC patients who were treated with TKIs (sunitinib, pazopanib and sorafenib) were enrolled in this prospective, non-interventional, multi-center observational study at 16 oncology centers across Turkey. Mean (SD) age was 61.3 (11.1) years and 74.8% were males. Data on duration of TKI treatment was the primary outcome measure. Additionally, overall response rate (ORR), progression free survival (PFS), overall survival (OS) and safety data were recorded. RESULTS: Median duration of treatment was 8.2 months at a median follow up of 17.9 months. ORR and disease control rate were 12.5% and 70.8%, respectively. Median PFS and OS were 7.5 months (95%CI: 6.4-10.4) and 27.3 months (95%CI: 17.6-27.3) with no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. The most common adverse events excluding progression-which was the protocol requirement were diarrhea (13.6%), asthenia (13.6%) and hand-foot syndrome (12.6%). Dose modifications were required in 30.5% of the patients and 15% discontinued TKIs because of toxicity. CONCLUSIONS: Our findings confirm the efficacy and safety profile of TKIs in the first-line treatment of mRCC patients intolerant to cytokine treatment. There was no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS.Trial registration: TURCOS ClinicalTrials.gov Identifier: NCT01585974. Registered April 25, 2012.

Factors Influencing Chemotherapy Goal Perception in Newly Diagnosed Cancer Patients.

Cancer patients who start receiving chemotherapy have difficulty in understanding the state of their disease, the prognosis, and the purpose of treatment. We used a survey to evaluate the extent of perception of chemotherapy goal among cancer patients. Two hundred sixteen cancer patients who received chemotherapy for the first time participated in the study. The presence of depression and anxiety was assessed using the "Hospital Anxiety and Depression Scale" (HAD). The consistency between the patients' perception of the chemotherapy goal and the physician's perception was described as "right," and the inconsistency was described as "wrong." Among the patients who participated in the survey, 53.2 % (n = 115) were receiving adjuvant treatment and 46.8 % (n = 101) were receiving palliative treatment for metastatic disease. The rate of right and wrong perception of the chemotherapy goal was 51.9 % (n = 108) and 32.2 % (n = 67), respectively, and the rate of confused patients was 18.9 % (n = 41). The level of education was shown to be the only parameter involved in accurate perception of the treatment purpose (hazard ratio (HR) = 0.444, p = 0.025, 95 % confidence interval (CI) 0.219-0.903). In this study, there was a 51.9 % consistency between the physician's perception and that of the patient regarding the purpose of treatment. We demonstrated that the level of education was the unique factor in accurate perception of chemotherapy goal among cancer patients.

Multicenter experience of adult medulloblastoma: A study of Anatolian Society of Medical Oncology (ASMO).

PURPOSE: Medulloblastoma (MB) is rarely seen in adults. For adjuvant therapy in adults the same therapy protocols used in pediatric cases are used. The present study retrospectively evaluated the data of MB patients who were treated in different Oncology Centers in Turkey. METHODS: The data of 60 adult patients with MB from 8 Oncology Centers diagnosed between 2005 and 2012 were retrospectively analyzed. RESULTS: The median patient age was 28.8 years (range 16-54). The administered chemotherapy included procarbazine+lomustin+vincristine (group A, N=31) and cyclophosphamide/ifosfamide+vincristine+cisplatin (group B, N=13). Median chemotherapy courses were 4 (range 1-8). Median progression free survival (PFS) was 76 months and median overall survival (OS) has not been reached in both groups. In young female patients and in those who received adjuvant chemotherapy, median PFS and OS were longer but without statistical significance. Mean PFS and OS were 65.9 months and 101.2 months in group A and 113.6 months and 141.6 months in group B, respectively. CONCLUSION: Improved survival results were obtained in women, in patients aged below 25 years, in those who underwent gross total excision (GTE) and in those who received adjuvant therapy with cyclophosphamide/ifosphamide.

The impact of immunohistochemical staining with ezrin-carbonic anhydrase IX and neuropilin-2 on prognosis in patients with metastatic renal cell cancer receiving tyrosine kinase inhibitors.

The identification of prognostic factors in patients with renal cell carcinoma (RCC) represents an area of increasing interest. In this retrospective study, we evaluated the prognostic role of carbonic anhydrase-IX, ezrin, and neuropilin in metastatic RCC patients. The expression of several biomarkers were measured by immunohistochemistry (IHC) in 45 patients with advanced stage RCC treated with second-line tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) after failure of interferon-alpha between January 2007 and June 2012. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on the survival. Age, ezrin and neuropilin-2 overexpression were found to be statistically significant factors (P < 0.05) for PFS in the univariate analysis. Ezrin and neuropilin-2 overexpression, hemoglobin and albumin level were statistically significant factors (P < 0.05) for OS in the univariate analysis. Multivariate analysis revealed that low expression of ezrin and neuropilin-2 was an independent prognostic factor for PFS and OS. The median PFS was 4 months for patients overexpressing neuropilin-2 versus 11 months for those with lower expression of neuropilin-2 (p = 0.033). The median OS was longer in patients with low levels of neuropilin-2 expression (26 months) compared to patients overexpressing neuropilin-2 (13 months) (p = 0.023). Increased expression of ezrin was associated with poor prognosis in patients treated with TKIs targeting VEGF (PFS, 3 vs 7 months; p = 0.012). High ezrin expression was associated with shorter OS (p = 0.009). This is the first study in the literature showing that neuropilin-2 and ezrin are related with prognosis in patients with advanced RCC.

Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites.

OBJECTIVE: Determination of human epidermal growth factor receptor-2 status in advanced gastric cancer is important in clinical decision making. In the trastuzumab for GC trial, trastuzumab-based therapy demonstrated a significant overall survival benefit in patients with human epidermal growth factor receptor-2-positive advanced gastric cancer. Human epidermal growth factor receptor-2 discordance in gastric cancer primary and its metastases has been long debated. The aim of the study was to evaluate the rate of human epidermal growth factor receptor-2 discordance and its effect on treatment decisions in advanced gastric cancer. METHODS: A total of 74 patients with advanced gastric cancer were included in the study. Both immunohistochemical staining and dual-color silver in situ hybridization were performed in all patients to evaluate the human epidermal growth factor receptor-2 status of the primary lesion and paired metastasis. RESULTS: The assessment of human epidermal growth factor receptor-2 status with the immunohistochemical staining method and dual-color silver in situ hybridization revealed a discordance rate of 9.5 and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a human epidermal growth factor receptor-2-negative status in primary tumor (immunohistochemical = 0, dual-color silver in situ hybridization = negative), the human epidermal growth factor receptor-2 status was positive for liver metastasis (immunohistochemical = 2+, dual-color silver in situ hybridization = positive). Trastuzumab was added to the chemotherapy regimen. CONCLUSIONS: In this study, we found a higher rate of human epidermal growth factor receptor-2 discordance between primary gastric tumor and metastatic lesions compared with the rates reported in previous studies. Detection of a human epidermal growth factor receptor-2-positive metastasis with a human epidermal growth factor receptor-2-negative primary tumor suggests that investigation of human epidermal growth factor receptor-2 is also required for the metastatic lesion and that trastuzumab could be administered in the case of a positive result.

Functional and morphological effects of systemic bevacizumab on cancer patients' eyes.

PURPOSE: To evaluate the morphological and functional short-term effects of systemic bevacizumab on healthy eyes of cancer patients morphologically and functionally. METHODS: The patients who underwent a chemotherapy regimen because of colon, lung, and breast cancer at the Department of Medical Oncology of the Gazi University School of Medicine between years 2010 and 2012 were included. All patients were administrated intravenous bevacizumab in three different dosages (5, 7.5, and 15 mg/kg per day) at 2- or 3-week intervals and a total of 6 to 18 courses in addition to regimens based on 5-fluorouracil, oxaliplatin, and irinotecan. After baseline ophthalmologic examination, patients were examined after the first course of chemotherapy and at the end of the protocol. Ophthalmologic evaluations included best-corrected visual acuity, color vision assessment, and ocular examinations with optical coherence tomography. RESULTS: Thirty-four eyes of 17 patients were enrolled. The mean (±SD) age of the patients was 53.64 (±11.09) years and median follow-up time was 9 months (range, 4 to 18 months). Seventy-six percent of the patients were diagnosed as having colon cancer and no significant change was identified in functional assessments such as best-corrected visual acuity or color vision or in morphological examinations with optical coherence tomography (central foveal thickness and retinal nerve fiber layer thickness parameters). Patients were divided into three groups based on the dosage of systemic bevacizumab infusions, and correlation between time-dependent changes in central foveal thickness, retinal nerve fiber layer thickness, and bevacizumab dosage was investigated and no significant correlation was detected. CONCLUSIONS: Repeated doses of systemic bevacizumab did not cause a deleterious effect on healthy eyes of cancer patients clinically, but further studies including histologic and biochemical analysis need to be conducted to reveal possible adverse effects.

Factors predicting the development of distant metastases in patients with head and neck squamous cell carcinoma: A retrospective study from a single centre.

PURPOSE: The presence of distant metastases (DMs) after the initial treatment of head and neck squamous cell carcinoma is associated with a poor outcome. The incidence of DMs in head and neck cancer is about 4-26%. The purpose of this study was to evaluate the prevalence of distant metastases and the factors predicting the development of DMs. METHODS: Between January 2000 and December 2010, 292 patients with head and neck squamous cell carcinoma were included in this study. RESULTS: Thirty three patients (11.3%) developed local recurrences, 27 patients (9.2%) developed DMs. The median post DMs survival was 23.4 months (range 1.8-229.1). The factors that significantly increased the risk of DMs were the presence of local recurrence (p=0.0001, OR:17.32, 95% CI:4.86-19.90), pathologically positive neck (p=0.008, OR:5.97, 95% CI: 3.25-10.45), and primary tumor localized in oral cavity or lip (p=0.035, OR:2.6, 95% CI:1.43-4.65). CONCLUSION: Patients with these factors should be considered candidates for adjuvant systemic treatment and evaluated for early detection of DMs during follow-up.

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.

Clear cell adenocarcinoma of the uterine cervix: a case report and review of the literature.

We report an extremely rare case of a patient with clear cell carcinoma of the cervix who had no history of in utero diethylstilbestrol (DES) exposure. Although clear cell adenocarcinoma is an uncommon tumor, it must be considered in the differential diagnosis in young women and children who have cervico-vaginal lesions even without in utero DES exposure history. We present the case of 2 girls, a 14-year-old and a 16-year-old, who were admitted to hospital because of intermittent vaginal bleeding and the presence of a cervical mass diagnosed as clear cell cervix carcinoma. Neither of them had a history of exposure to DES.

Factors predicting recurrence in patients with grade III glial tumors: impact of adjuvant temozolomide on recurrence.

PURPOSE: The purpose of this study was to evaluate the clinicopathological features of patients with grade III glial tumors associated with recurrence after treatment. METHODS: A retrospective analysis was carried out on 67 patients with grade III glial tumors between May 2007 and June 2013. Data were retrieved from patient electronic medical records and paper charts. RESULTS: The patient median age was 43 years (range 19-707 rpar;. Of these, 50.7% (N=34) had anaplastic astrocytoma, 29.9% (N=20) anaplastic oligoastrocytoma and 19.4% (N=13) anaplastic oligodendroglioma. Among these 67 patients, 41 (61.2%) developed local recurrence. Fifty seven of them (80.6%) received radiotherapy (RT) with concomitant temozolomide. Of these patients, 14 (20.9%) received RT with concomitant temozolomide alone, and 43 (64.2%) were treated with concomitant chemoradiotherapy followed by adjuvant temozolomide. Time to recurrence (TTR) of patients who received adjuvant temozolomide after concomitant chemoradiation (TTR=14 months, 95% CI 9.3-22.77 rpar; as initial treatment for grade III glial tumors was not superior to RT with concomitant temozolomide alone (TTR=21 months, 95% CI 14.8-35.2; p=0.224) In multivariate analysis, histologic subtype (p=0.015), age (p=0.019) and presence of neurologic symptoms (p=0.021) were independent predictive factors of recurrence. CONCLUSION: This analysis demonstrated that histologic subtype, age and presence of neurologic symptoms were significantly associated with recurrence in patients with grade III glial tumors. Adjuvant temozolomide was not significantly associated with recurrence in patients with grade III glial tumors. The identification of these predictors may be important for the patient follow-up and better treatment modifications.

Treatment modalities in primary gastric lymphoma: the effect of rituximab and surgical treatment. A study by the Anatolian Society of Medical Oncology.

AIM OF THE STUDY: Gastrointestinal lymphoma is the most common type of extranodal lymphoma and commonly involved site is the stomach. We have compared the superiority between treatment modalities for primary gastric lymphoma and we want to investigate efficacy of rituximab in gastric lymphoma. MATERIAL AND METHODS: Between April 2002 and December 2011, 146 patients with a histologically confirmed primary gastric lymphoma, initially diagnosed at eight different Cancer Centers within Turkey were evaluated retrospectively. According to the treatment modality, the patients were divided into chemotherapy (CT) alone, chemotherapy and radiotherapy (CRT), surgery and chemotherapy (SCT), surgery along with chemotherapy and radiotherapy (SCRT), and surgery (S) alone groups. RESULTS: Median follow-up period was 25.5 months. The 5-year EFS (event free survival) and OS (overall survival) rates for the patients were 55% and 62.3% respectively. In Log rank analysis of OS and EFS, we have identified levels of albumin and hemoglobine, IPI score, stage at diagnosis as factors influencing survival. In multivariate analysis of OS and EFS, only albumin and stage at diagnosis were factors independently contributing to survival. There was no statistically significant difference in terms of survival between different treatment modalities (p = 0.707 in EFS and p = 0.124 in OS). In analysis of patients treated with chemotherapy alone, there was no a statistically significant difference in terms of EFS and OS between chemotherapy regimens with or without rituximab in localized and advanced stage groups (p = 0.264 and p = 0.639). There was no statistical difference in survival rate (EFS and OS) between surgical or non-surgical treatment modalities for localized/advanced stage gastric lymphoma groups (p = 0.519 / p = 0.165). CONCLUSIONS: There are several treatment options due to similar results in different treatment modalities. Also benefit of rituximab treatment in gastric lymphoma is still a controversial subject. Additional prospective trials are definitely required in order to clarify use of rituximab in treatment of extranodal gastric lymphoma.

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.

Results of adjuvant FOLFOX regimens in stage III colorectal cancer patients: retrospective analysis of 667 patients.

OBJECTIVE: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. METHODS: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. RESULTS: The median age of the patients was 56 years (range 17-78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1-79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. CONCLUSION: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.

Bevacizumab-containing chemotherapy is safe in patients with unresectable metastatic colorectal cancer and a synchronous asymptomatic primary tumor.

OBJECTIVE: Surgical resection of asymptomatic primary colorectal cancer in patients presenting with synchronous unresectable metastatic disease is controversial. Concerns and controversies remain over combining cytotoxic chemotherapy with bevacizumab in this patient population. METHODS: We identified medical records of 99 patients with synchronous metastatic primary colorectal cancer who received chemotherapy with bevacizumab as their initial treatment. The incidence of subsequent use of surgery and surgical outcomes were recorded. Patients were also assessed for overall survival. RESULTS: Patients who received bevacizumab-containing chemotherapy for synchronous metastatic primary colorectal cancer were divided into the non-surgery and surgery groups according to the resection status of their asymptomatic primary tumor. In the non-surgery group, two patients (4.4%) underwent additional surgery, while three patients (5.7%) required surgery for rectovesical fistula in the surgery group. The median overall survival was 17 months for the non-surgery group (95% CI: 10.6-23.3 months) and 23 months for the surgery group (95% CI: 21.3-24.6 months; P = 0.322). CONCLUSIONS: This study utilizing chemotherapy with bevacizumab did not result in an increased rate of morbidity related to the unresected primary tumor. Survival is not compromised by leaving the primary colon tumor intact.

Prognostic factors for recurrence-free survival in patients with HER2-positive early-stage breast cancer treated with adjuvant trastuzumab.

BACKGROUND: The objective of this study was to identify prognostic factors affecting the recurrence-free survival (RFS) in patients who received a 52-week trastuzumab therapy for HER2-positive early stage breast cancer (EBC). PATIENTS AND METHODS: The medical records of all patients with EBC from 10 centers were analyzed. Pathologic and clinical tumor characteristics were evaluated in 424 female patients who received 52 weeks of adjuvant trastuzumab for HER2-positive EBC. Survival was estimated using the Kaplan-Meier method. Univariate analyses of RFS were performed with the log-rank test. Independent prognostic and predictive factors affecting RFS were assessed by Cox regression analysis. RESULTS: Median follow-up time was 33.1 months (range 9.2-75.9 months). 3-year RFS and overall survival were 87 and 97%, respectively. In multivariate analysis, patients aged 70 years or over (p = 0.017, relative risk (RR) 2.7, 95% confidence interval (CI) 1.19-6.13), patients with > 9 positive lymph nodes (p = 0.001, RR 2.52, 95% CI 1.42-4.46), and those with progesterone receptor-negative tumors (p = 0.006, RR 2.33, 95% CI 1.27-4.27) had worse RFS. CONCLUSION: In spite of a 52-week adjuvant trastuzumab treatment, classic poor prognostic factors for invasive EBC remained as such in patients with HER2-positive EBC.

Efficacy of sunitinib in Turkish patients with gastrointestinal stromal tumors; retrospective multicenter experience.

BACKGROUND/AIMS: Sunitinib is a multi-targeted thyrosine kinase receptor inhibitor used in patients with advanced gastrointestinal stromal tumours (GISTs). We evaluated the efficacy and tolerability of sunitinib therapy in Turkish patients with GISTs. METHODOLOGY: Between January 2001 and April 2012, 57 patients who had progressive disease or experienced unacceptable toxicity during imatinib treatment from multiple centers were investigated retrospectively. RESULTS: Thirty-three patients were male and 24 were female. The median age was 55 years (range; 16-84 years). Thirty-eight of the patients received imatinib for longer than 12 months, 13 patients received for 6-12 months, and 6 patients received for less than six months. The clinical benefit of sunitinib was 73.7%. Treatment-related adverse events were reported in 78% of the patients. Adverse events were generally mild to moderate in intensity. The median progression free survival (PFS) and overall survival (OS) of the patients that received sunitinib were 10.8 months and 23.9 months, respectively. The time of imatinib usage and response to sunitinib were independent prognostic factors for PFS and OS. Also, tumor size was an independent prognostic factor for PFS. CONCLUSIONS: Sunitinib is an effective treatment in Turkish patients with GISTs, with a clinical benefit of 73.7% and shows an acceptable tolerability.

Prognostic factors in gastrointestinal stromal tumors: multicenter experience of 333 cases from Turkey.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. In an attempt to survey the approximate incidence, clinicopathological characteristics, and immunophenotypic features of GISTs in Turkey, we conducted a clinicopathological and immunohistochemical analysis of GISTs. METHODOLOGY: Three hundred and thirty-three patients with GIST from nine institutions in Turkey were retrospectively evaluated. RESULTS: Between January 2001 and March 2011, a total of 333 patients with GISTs were included; of these, 204 (61.2%) were male and 129 (38.8%) were female. The median age was 55 years (range; 22-102 years). At the median follow-up of 26 months (range; 4-166 months), the 1-, 3- and 5-year OS rates of the 333 patients were 96.9%, 85.8% and 78.5%, respectively. The 5-year DFS rate was 40%. The 5-year OS rate and median OS time for the patients with R0 resection were significantly higher than for patients with metastatic diseases (79.7 vs. 75.7% and not reached vs. 115 months, respectively, p=0.04). CONCLUSION: Although our results should be confirmed by prospective studies, we believe that they contribute to the literature because the study included both resectable and metastatic or unresectable GIST patients and multicenter findings from Turkey.

The role of positron emission tomography with 18F-fluorodeoxyglucose in nodal staging of clinical and radiological N0 head and neck cancers.

The objective of the study was to evaluate the impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) imaging on nodal staging for head and neck cancers. This was a retrospectively analyzed single institution study. The study population consisted of 36 patients with head and neck cancers who were evaluated with PET/CT and went on to neck dissection. All of them had clinically and radiographically negative neck (N0) and each patient underwent PET/CT imaging before undergoing selective neck dissection for N0 disease. Tissues were submitted for histopathologic examination and were oriented for the pathologist to permit correlation between the histopathologic findings and the imaging results. The sizes of the lymph nodes and the maximum standardized uptake values (SUVmax) measured from PET/CT images were compared with the histopathologic findings. All primary tumors were visualized with PET/CT. On histopathological examination, 19 patients had positive and 17 patients had negative lymph nodes. Receiver operating characteristic analyses were used to predict the optimal corrected SUVmax cutoffs; the optimal value was 2.95 for respective outcomes of lymph node involvement. This cutoff value yielded 84.2% sensitivity and 76.5% specificity for nodal-level staging. PET/CT proved to be accurate in 27 (75%) patients and inaccurate in 9 (25%) patients. PET/CT was a valuable tool to assess nodal stage of head and neck cancers, and should be considered before surgical treatment.

Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP)-treated DLBCL cases. METHODS: Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R-CHOP-treated patients. RESULTS: MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P = .01), especially for the cases with GC phenotype (P = .009). BCL6 rearrangement also predicted significantly shorter overall survival (P = .04), especially for the non-GC phenotype (P = .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P = .004) and MYC rearrangement (P = .009) were independent poor prognostic factors. CONCLUSIONS: Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high-risk patients with poor prognosis.

Sunitinib- and sorafenib-induced nephrotic syndrome in a patient with gastrointestinal stromal tumor.

OBJECTIVE: To report a case of nephrotic syndrome (NS) induced by both sunitinib and sorafenib therapy. CASE SUMMARY: A 61-year-old woman with metastatic gastrointestinal stromal tumor (GIST) presented with NS and hypertension following therapy with sunitinib 400 mg/day. Because of grade 3 toxicity, the drug was discontinued. After sunitinib discontinuation, NS and hypertension resolved. However, NS recurred on rechallenge. A similar picture developed following therapy with sorafenib 800 mg/day. A renal biopsy revealed a focal segmental glomerulosclerosis (FSGS). A few months after sorafenib cessation, resolution of NS and hypertension was again achieved. DISCUSSION: Several cases of NS have been reported among patients receiving sunitinib and sorafenib. However, renal histopathologic data were obtained in only a few patients. Although biopsy-proven cases of FSGS associated with sunitinib have been reported, this is, to our knowledge, the first reported case of biopsy-proven FSGS associated with sorafenib. The Naranjo probability scale indicated probable causality for NS developing with sorafenib, and definite causality with sunitinib. The clinical and histopathologic findings have led us to agree with the class effect proposal that all antiangiogenic drugs share a similar toxicity profile. Evidence supporting this hypothesis includes worsening of hypertension and proteinuria by both drugs, with full recovery occurring within a few months after cessation of the drugs, which favors the role of vascular endothelial growth factor receptor inhibition in FSGS development. CONCLUSIONS: The clinical adverse spectrum of antiangiogenic drugs may be broader than initially observed because of a lack of renal biopsy data and routine screening for proteinuria. It can be speculated that proteinuria, as well as hypertension, is a class effect of all antiangiogenic drugs.