BRAF Inhibitor Therapy-Related Encephalitis in a Patient with Metastatic Melanoma.

INTRODUCTION: BRAF inhibitors such as encorafenib and vemurafenib in combination with MEK inhibitors are commonly used for the treatment of patients with BRAF V600-mutant melanoma. CASE PRESENTATION: A patient with relapsed metastatic melanoma with a BRAF V600 mutation was started on treatment with vemurafenib and cobimetinib. Within 2 weeks of treatment start, he was hospitalized and diagnosed with encephalitis through a lumbar puncture and treated with corticosteroids, with subsequent normalization of cerebrospinal fluid (CSF) findings. When he recovered and was switched to encorafenib treatment, the same symptoms recurred, and the patient was treated with high-dose steroids and intravenous immunoglobulin, again with improvement in his CSF. He has not had a relapse of his symptoms since BRAF inhibitor treatment was permanently discontinued. CONCLUSION: This is the first known report of a patient who has developed encephalitis because of treatment with BRAF inhibitors.

Modified Glasgow Prognostic Score, Prognostic Nutritional Index and ECOG Performance Score Predicts Survival Better than Sarcopenia, Cachexia and Some Inflammatory Indices in Metastatic Gastric Cancer.

Background: Gastric carcinoma (GC) patients usually present with locally advanced or metastatic disease; therefore treatment aim is mainly palliation. In this study our purpose is to analyze the prognostic values of the sarcopenia index (SI), cachexia index (CIn) and other inflammatory indexes (advanced lung cancer inflammation index [ALI], modified Glasgow Prognostic Score [mGPS], prognostic index [PI], prognostic nutritional index [PNI] and neutrophil-to-lymphocyte ratio [NLR]) in metastatic GC patients.Methods: Data from the files of metastatic GC patients, who applied to Medical Oncology outpatient clinic in Marmara University Pendik Education and Research Hospital between January 2011 and June 2016, were retrospectively reviewed. Five hundred seventy patients with gastric cancer were detected. Exclusion criteria were the inability to reach the patient surveys for prognostic index calculations, the presence of additional comorbidities to affect the laboratory parameters, and the absence of metastatic disease. Finally, 87 of these patients were included in this study. For SI calculation L3 level muscle area was measured from patients' computed tomography (CT) by a radiologist. SI reference value was obtained from western-EGWSOP (The European Working Group on Sarcopenia in Older People) and eastern (Harada Y, et al.) sources separately, as Turkey doesn't have a reference value for SI. NLR cutoff value was accepted as the median value of patients' NLR measurements. Statistical analysis was conducted using SPSS. Kaplan-Meier and Cox regression models were used to assess independent prognostic factors. The area under the curve was used to compare the prognostic value of indexes.Results: The median length of follow-up of 87 patients was nine months (1-64 mo,/s), and 78 patients died during follow-up. Fifty-nine patients were male (63%), and the median age was 62 (range, 23-88). According to univariate analysis high mGPS and PI score, PNI level <45, NLR level ≥ 3.41, ALI level <18, CI level under 35, SI (Harada Y, et al) ≤44.5 for males and ≤36.5 for females, ECOG score ≥ 2, weight loss more than 10% during last 6 mo, BMI under 24 were poor prognostic factors. Age, gender, having multiple organ metastasis, history of gastric surgery, positivity C-erb-B2, SI (EGWSOP) ≤52.4 for males, and ≤38.4 for females did not have any impact on survival. According to multivariate analysis, high mGPS (score 2) (HR 2,494, 95% CI 1.25-4 .94, p = 0.02), PNI (score 1) (HR 4.2, 95% CI 1.73-10.1, p < 0.001) and ECOG score (≥2) (HR 1.541, 95% CI 1,089-4,214, p = 0.004) have been found to be independent prognostic factors which are determining the survival. mGPS was found to be more valuable than other indexes for predicting mortality by measuring the AUC with ROC analysis.Conclusions: In our study, mGPS, PNI and ECOG score were independent indicators for shorter survival in metastatic gastric cancer patients. mGPS and PNI, which can be done by using only serum CRP, albumin level and complete blood count, might be inexpensive, practical and beneficial to use in routine clinical practice to determine survival.

Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience.

PURPOSE: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. METHODS: Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. RESULTS: At the time of diagnosis, the median age was 48 (17-77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1-68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). CONCLUSION: Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.

Treatment Options for Advanced Melanoma After Anti-PD-1 Therapy.

PURPOSE OF REVIEW: While anti-PD-1 antibodies have been a breakthrough in the treatment of patients with advanced melanoma, a substantial proportion of patients are still refractory to or progress after treatment with anti-PD-1 immunotherapy. Here, we review the post anti-PD-1 therapy alternatives that may be possible for patients with unresectable or metastatic stage 3 or 4 melanoma. RECENT FINDINGS: Currently available treatment options include BRAF-targeted and MEK inhibitor-targeted therapies for those with BRAFV600 mutant melanoma, while for patients with BRAF-WT melanoma or those who have already received prior BRAF-targeted therapy, options include anti-CTLA-4 therapy, alone or in combination with anti-PD-1 therapy, or for selected patients, clinical trials that may incorporate other immune checkpoint inhibitors or co-stimulatory agonists, oncolytic virotherapies, adoptive cellular therapies, or other novel agents. Participation in clinical trials is critical in order to delineate what more effective treatment options are and which group of patients after receiving prior anti-PD-1 therapy.

How long should we continue crizotinib in ALK translocation-positive inflammatory myofibroblastic tumors? Long-term complete response with crizotinib and review of the literature.

INTRODUCTION: Inflammatory myofibroblastic tumor is a rare disease which is typically seen in children and young adults. Approximately half of the inflammatory myofibroblastic tumors contain translocations that result in over-expression of anaplastic lymphoma kinase gene. Herein, we present two anaplastic lymphoma kinase-positive cases with long-term remission with crizotinib. We do not know how long these therapies need to be continued. CASE REPORTS: We present two cases of inflammatory myofibroblastic tumor treated with anaplastic lymphoma kinase inhibitor therapies: an 8-year-old Turkish boy and a 21-year-old Caucasian man. MANAGEMENT AND OUTCOME: Two cases, both with good tumor control under crizotinib, but one who progressed on drug holiday, responded again to the same drug, and had a very short period of response after restarting crizotinib. CONCLUSION: A molecular-targeted drug (anaplastic lymphoma kinase inhibitor) was found to be extremely effective as selective therapy for inflammatory myofibroblastic tumor with anaplastic lymphoma kinase translocation. Here, we want to emphasize the continuation of this treatment after achieving a good response until progression or a major side effect.

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.

The impact of radiotherapy on quality of life for cancer patients: a longitudinal study.

PURPOSE: The aim of this study was to assess for changes in quality of life (QOL) among cancer patients who undergo radiotherapy (RT) and to identify factors that influence QOL in this group. MATERIALS AND METHODS: Three hundred sixty-seven cancer patients who received curative RT were investigated using the EORTC QLQ-C30 questionnaire at the start of RT, end of RT, and 1 and 6 months post-RT. RESULTS: The patients were 49 % women, 51 % men, and median age at diagnosis was 57 years (range, 16-86 years). Compared to pre-RT, at the end of RT, the global health status score (p < 0.001), nausea/vomiting (p < 0.001), and apetite loss scores (p < 0.001) were significantly poorer. Compared to the end of RT, at 1 and 6 months post-RT, global health status, all functional, and all symptom scores were significantly improved (p < 0.001). Patient sex influenced scores for pain (p = 0.036), appetite loss (p = 0.027), and financial difficulty (p = 0.003). Performance status influenced scores for global health status (p = 0.006), physical functioning (p < 0.001), cognitive functioning (p = 0.001), and role functioning (p = 0.021). Comorbidity influenced fatigue score (p < 0.001). Cancer stage influenced scores for physical functioning (p = 0.001), role functioning (p = 0.010), and fatigue (p < 0.001). Treatment modality (chemoRT vs. RT alone) influenced scores for physical functioning (p = 0.016), fatigue (p < 0.001), nausea/vomiting (p = 0.009), and appetite loss (p < 0.001); and RT field influenced scores for nausea/vomiting (p = 0.001), appetite loss (p = 0.003), and diarrhea (p = 0.037). Radiotherapy dose functioning (p < 0.001), cognitive functioning (p < 0.001), social functioning (p < 0.001), fatigue (p < 0.001), and pain (<60 vs ≥60 Gy) had an effect on scores for physical functioning (p < 0.001), role functioning (p < 0.001), emotional (p < 0.001), insomnia (p < 0.001), constipation (p < 0.001). CONCLUSION: While RT negatively affects cancer patients' QOL, restoration tends to be rapid and patients report significant improvement by 1 month post-RT. Various patient- and disease-specific factors and RT modality affect QOL in this patient group. We advocate measuring cancer patients' QOL regularly as part of routine patient management.

Can assessment of disease burden and quality of life based on mobility level in patients with end-stage cancer provide an insight into unmet needs? An exploratory cross-sectional study.

PURPOSE: The purpose of this study was to: 1) investigate the differences in the needs of end-stage cancer who can move independently, using mobility aids (MA), or are bedridden; and 2) determine the effects of these different mobility levels on the patients' current quality of life (QoL), fatigue, and mental conditions. METHODS: The study employed an exploratory prospective cross-sectional study design, which was carried out in two hospitals. The study included 99 end-stage cancer. The mobility levels of the patients were evaluated in three groups: Group 1: bedridden; Group 2: mobile with MA; and Group 3: ambulatory (under supervision or fully independent). A core cancer-specific questionnaire-integrating system for assessing health-related QOL (EORTC-QLQ-C15-PAL), the Piper Fatigue Scale (PFS), and the Hospital Anxiety-Depression scale were utilized.The median age was 60years (31-83). Cancer types were as follows: gastrointestinal (45.5%), lung (38.4%), breast (4%), genitourinary system (4%), and others (8%). Forty-two percent of the patients were completely bedridden, 42.2% used MA, and 15.2% were independently ambulatory. The EORTC QLQ-C15-PAL physical (=.000) and emotional function values (=.029) differed among mobilization statuses. There was a significant difference among mobilization groups, in terms of behavioral values, in the PFS (=.006). The depression rate in the independent ambulatory group was lower than in the bedridden and MA groups (=0.011; =0.004).  p p p p1  p2 . CONCLUSION: Health-related QoL, fatigue level, and emotional state vary in end-stage cancer who undergo evaluations according to their mobility levels. These patients should be assessed comprehensively, and treatment plans should be organized carefully, with a multidisciplinary approach.

Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection.

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.

Results of treating primary pulmonary sarcomas and pulmonary carcinosarcomas.

OBJECTIVE: Primary pulmonary sarcomas (PPS) and pulmonary carcinosarcomas (PCS) are rare aggressive lung malignancies. We reviewed our 21-year experience with the surgical and nonsurgical treatment of both tumors, comparing their clinical, histopathologic, and treatment results. METHODS: All patients with PPS or PCS who underwent surgical and nonsurgical treatment between 1998 and 2019 at our cancer center were retrospectively reviewed. Multivariable Cox proportional hazards model was constructed. RESULTS: In total, 100 patients were analyzed: 45 with PPS and 55 with PCS. Among patients with PPS, 31 of 45 (69%) underwent surgery with 1 (3%) operative mortality. For patients with PCS, 29 of 55 (53%) underwent surgery with no operative mortality. Patients with PPS were younger than PCS (P < .01). Fewer patients were smokers among PPS (58%) versus PCS (93%) (P < .01). For resected PPS, mean tumor size was 8.2 ± 4.1 cm (range 2.2-18.0) compared with 10.1 ± 5.0 cm (range 3.9-17.0) for unresected PPS. Tumor size for resected PCS was 6.2 ± 2.6 cm (range 2.0-10.5) versus 6.8 ± 3.5 cm (range 1.2-13.5) for unresected PCS. Of resected patients, 5 of 31 (16%) with PPS and 9 of 29 (31%) with PCS were node positive. Overall survival estimates were as follows: for PPS, median survival and 5-year overall survival for resected versus unresected cases were 39.6 months/28.7% versus 4.9 months/7.8%. For PCS, survival estimates were 23.6 months/31.0% versus 14.9 months/28.2%, respectively. In multivariable analyses (N = 100), age, smoking history, histology, and surgery were risk factors of survival. CONCLUSIONS: At initial evaluation, PPS and PCS presented with large-sized tumors and usually were not stage I. Surgery had a positive impact on survival among patients with PPS. Whenever feasible, surgical resection, even in locally advanced disease, may yield long-term survival in these aggressive lung tumors, although the level of evidence is low.

Merkel cell carcinoma in Turkey: A multicentric study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin. In this study, we aimed to evaluate the clinicopathologic characteristics, treatment outcomes, and survival of MCC cases in Turkey. MATERIALS AND METHODS: The patients diagnosed with MCC between 1999 and 2018 at twenty different centers in Turkey were included in the study. Patient and tumor characteristics and adjuvant and metastatis treatment outcomes were analyzed retrospectively. RESULTS: The median age of totally 89 patients was 70 (26-93). The most common primary location was lower limbs (n = 29, 32.5%). Immunohistochemically, CK20 positivity was present in 59 patients (66.3%). Only two patients had secondary malignancy. The majority of the patients (n = 76, 85.4%) were diagnosed at the localized stage. Surgery was performed for all patients in the early stage, and adjuvant radiotherapy or/and chemotherapy was applied to 52.6% (n = 40) of nonmetastatic patients. The median follow-up was 29 months. Recurrence developed in 21 (27.6%) of the 76 patients who presented with local or regional disease. Two-year disease-free survival (DFS) was 68.1% and 5-year DFS was 62.0% for localized stage. The 5-year DFS was similar for patients receiving adjuvant treatment (chemotherapy, radiotherapy, or sequential chemoradiotherapy) and without adjuvant therapy (P > 0.05). Two-year overall survival in patients who presented with localized disease was 71.3% and 18.5% in metastatic patients (P < 0.001). In the metastatic stage, platinum/etoposide combination was the most preferred combination regimen. Median progression-free survival (PFS) in first-line chemotherapy was 7 months (95% confidence interval: 3.5-10.5 months; standart error: 1.78). CONCLUSIONS: Although MCC is rare in Turkey, the incidence is increasing. Gender, CK20 status, tumor size, lymph node involvement, and adjuvant treatment were not associated with recurrence.

Neoadjuvant BRAF-targeted therapy in regionally advanced and oligometastatic melanoma.

Current management of locoregional and oligometastatic melanoma is typically with surgery; however, some patients are unable to undergo resection due to location/size of their tumors and/or the anticipated morbidity of the surgery. While there are currently no established guidelines for neoadjuvant therapy in melanoma, neoadjuvant BRAF-targeted therapy may make resection more feasible. A retrospective analysis was conducted of 23 patients with BRAFV600-mutant, stage III/IV melanoma treated with BRAF-targeted therapy prior to surgery, with no adjuvant treatment. Surgical specimens, preoperative imaging, and clinical outcomes were evaluated. Results: Ten of 23 patients (44%) attained a pathologic complete response (pCR), with no correlation between RECIST response based on preoperative imaging and pathologic response. After a median of 43-month follow-up, only 1 patient (10%) with a pCR recurred, while 8 of 13 (62%) patients without a pCR recurred. Patients with a pCR had significantly improved relapse-free (RFS) and overall survival (OS) compared to patients with residual tumor. Neoadjuvant BRAF-targeted therapy is associated with a high pCR rate in patients with stage III-IV melanoma, which may correlate with improved RFS and OS.

Assessment of survival and prognostic factors in metastatic colorectal cancer patients treated with first-line bevacizumab-based therapy.

PURPOSE: Colorectal cancer (CRC) is a significant cause of cancer mortality worldwide. Survival has improved with bevacizumab in metastatic CRC treatment. Our purpose was to analyse survival and prognostic factors in metastatic CRC patients treated with first-line bevacizumab-based treatment. METHODS: Files of CRC patients were examined retrospectively and 360 patients treated with first-line bevacizumab were included. Objective response rates (ORRs), median progression-free and overall survival (PFS and OS) of the patients were calculated. Survival was analyzed with the Kaplan-Meier method. Log-rank test and Cox regression model were used for univariate and multivariate analyses, respectively. RESULTS: Median age at diagnosis was 59.5 years. Of the patients 74.4% had initially stage IV disease. Median PFS was 8.5 months, median OS 25.3 months and ORR was 51.4%. ORRs, median PFS and OS of KRAS mutant and wild-type or unknown patients were statistically similar. In left-sided disease, median PFS and OS (9.6 and 27.1 months) were superior compared to right-sided disease (7.3 and 19.4 months) (p=0.005 and 0.02, respectively). Primary disease location, histopathologic grade, primary surgery and metastasectomy affected OS significantly. Histopathologic grade (hazard ratio=1.77, p=0.002) and metastasectomy (hazard ratio=0.48, p=0.001) were independent prognostic factors. CONCLUSIONS: Our study confirmed that after bevacizumab-based treatment, KRAS status might not be a prognostic factor. We have also shown that left CRC have more favorable outcomes than right CRC in bevacizumab therapy. Additionally, even in metastatic setting histopathologic grade of the primary CRC together with metastasectomy are independent prognostic factors.

Leveraging transcriptional dynamics to improve BRAF inhibitor responses in melanoma.

BACKGROUND: Melanoma is a heterogeneous tumour, but the impact of this heterogeneity upon therapeutic response is not well understood. METHODS: Single cell mRNA analysis was used to define the transcriptional heterogeneity of melanoma and its dynamic response to BRAF inhibitor therapy and treatment holidays. Discrete transcriptional states were defined in cell lines and melanoma patient specimens that predicted initial sensitivity to BRAF inhibition and the potential for effective re-challenge following resistance. A mathematical model was developed to maintain competition between the drug-sensitive and resistant states, which was validated in vivo. FINDINGS: Our analyses showed melanoma cell lines and patient specimens to be composed of >3 transcriptionally distinct states. The cell state composition was dynamically regulated in response to BRAF inhibitor therapy and drug holidays. Transcriptional state composition predicted for therapy response. The differences in fitness between the different transcriptional states were leveraged to develop a mathematical model that optimized therapy schedules to retain the drug sensitive population. In vivo validation demonstrated that the personalized adaptive dosing schedules outperformed continuous or fixed intermittent BRAF inhibitor schedules. INTERPRETATION: Our study provides the first evidence that transcriptional heterogeneity at the single cell level predicts for initial BRAF inhibitor sensitivity. We further demonstrate that manipulating transcriptional heterogeneity through personalized adaptive therapy schedules can delay the time to resistance. FUNDING: This work was funded by the National Institutes of Health. The funder played no role in assembly of the manuscript.

Treatment Approaches in 102 Elderly Patients With Non-Small Cell Lung Cancer.

BACKGROUND: The life expectancy and presence of co-morbidities cause reservations in treatment decisions for elderly patients with cancer. In this study, we retrospectively evaluated 102 patients who are considered as middle-old aged (aged 75 - 84) by gerontologists. METHODS: Medical records of patients were reviewed. One hundred and two patients with a diagnosis of non-small cell lung cancer (NSCLC) whose follow-up ended with death between March 2006 and May 2013 were examined. RESULTS: The median age at diagnosis was 77 (75 - 85) years. Thirty-three patients (67.6%) were over 80 years old. The number of patients with metastasis was 57 (55.8%). Forty-two (41.2%) patients had stage IIIA and IIIB disease. Fifteen of the metastatic patients (26.3%) were given chemotherapy, while 12 of the non-metastatic patients (26.6%) were given chemotherapy. Of the non-metastatic patients, 25 (55.6%) were treated with radiotherapy, and five (11.1%) were treated with chemotherapy. The median duration of follow-up was 4 (1-55) months. Progression-free survival (PFS) was 4 months in non-metastatic patients, and 3 months in metastatic patients. Overall survival (OS) was 4 months. OS rates for 1 and 2 years were 10% and 2%. CONCLUSION: Chemotherapy and radiotherapy may be administered even to patients of this age group. The beneficial effect of chemotherapy in patients with metastasis on OS is an important finding of our study.

Hypersensitivity and tumor lysis syndrome associated with cetuximab treatment: should we be afraid?

The majority of the chemotherapy agents in use today cause various infusion reactions, from mild flushing to life-threatening events. The frequency of the reported hypersensitivity reactions induced by cetuximab varies between 3% and 22%. It is recommended in the literature to stop the infusion and replace cetuximab with panitumumab in case of hypersensitivity reactions observed during the treatment of colon cancer. Tumor lysis syndrome (TLS) may occur in colorectal cancers with heavy tumor load. Tumor lysis syndrome may be life-threatening. In our patient with widespread bone and liver metastases, treatment continued with cetuximab as a combination therapy with irinotecan in spite of the hypersensitivity and TLS led to a complete treatment response. The complete response observed after 3 months through continued therapy in our patient may present an example supporting treatment with cetuximab in spite of severe reactions.

A Case of Multifocal Skin Metastases from Lung Cancer Presenting with Vasculitic-type Cutaneous Nodule.

Although cutaneous metastasis occurs usually at the terminal stage of the disease, it may be rarely concurrent with the diagnosis and may also present as the first sign of the illness. A 55-year-old male patient presented with vasculitic-type cutaneous nodular lesions and a necrotic distal phalangeal lesion developed over the last month. He was a tradesman and smoked 40 packets year. On physical examination, he was found to have multiple cutaneous lesions on the skin of the face, limbs, neck, scalp, dorsal side, fingers, subungual side, right leg, and feet. A skin lesion punch biopsy was performed and squamous cell carcinoma metastasis was detected. He was diagnosed as having squamous cell lung cancer with bronchoscopic biopsy. Although it is very rare, cutaneous metastases that is concurrent with the diagnosis of lung cancer may be the first sign of the disease. In patients with suspicious skin lesions, the patient's age, smoking history, and other symptoms should be evaluated and a biopsy should be performed.

Potential impact of atelectasis and primary tumor glycolysis on F-18 FDG PET/CT on survival in lung cancer patients.

BACKGROUND: Atelectasis is an important prognostic factor that can cause pleuritic chest pain, coughing or dyspnea, and even may be a cause of death. In this study, we aimed to investigate the potential impact of atelectasis and PET parameters on survival and the relation between atelectasis and PET parameters. MATERIALS AND METHODS: The study consisted of patients with lung cancer with or without atelectasis who underwent (18)F-FDG PET/CT examination before receiving any treatment. (18)F-FDG PET/CT derived parameters including tumor size, SUVmax, SUVmean, MTV, total lesion glycosis (TLG), SUV mean of atelectasis area, atelectasis volume, and histological and TNM stage were considered as potential prognostic factors for overall survival. RESULTS: Fifty consecutive lung cancer patients (22 patients with atelectasis and 28 patients without atelectasis, median age of 65 years) were evaluated in the present study. There was no relationship between tumor size and presence or absence of atelectasis, nor between presence/absence of atelectasis and TLG of primary tumors. The overall one-year survival rate was 83% and median survival was 20 months (n=22) in the presence of atelectasis; the overall one-year survival rate was 65.7% (n=28) and median survival was 16 months (p=0.138) in the absence of atelectasis. With respect to PFS; the one-year survival rate of AT+ patients was 81.8% and median survival was 19 months; the one-year survival rate of AT- patients was 64.3% and median survival was 16 months (p=0.159). According to univariate analysis, MTV, TLG and tumor size were significant risk factors for PFS and OS (p<0.05). However, SUVmax was not a significant factor for PFS and OS (p>0.05). CONCLUSIONS: The present study suggested that total lesion glycolysis and metabolic tumor volume were important predictors of survival in lung cancer patients, in contrast to SUVmax. In addition, having a segmental lung atelectasis seems not to be a significant factor on survival.

Higher Ki67 expression is associates with unfavorable prognostic factors and shorter survival in breast cancer.

BACKGROUND: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of this study was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2 and hormone receptor expression status in breast cancers. MATERIALS AND METHODS: Clinical and pathological features of the patients with breast cancer were retreived from the hospital records. RESULTS: In this study, 163 patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20% and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001), estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymph node positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free and overall survival compared to those of higher Ki67 levels. CONCLUSIONS: High Ki67 expression is associated with ER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The level of Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.

Survival analysis and prognostic factors for neuroendocrine tumors in Turkey.

BACKGROUND: This study aimed to determine the demographical distribution, survival and prognostic factors for neuroendocrine tumors monitored in our clinic. MATERIALS AND METHODS: Data for 52 patients who were admitted to Cumhuriyet University Medical Faculty Training Research and Practice Hospital Oncology Center between 2006 and 2012 and were diagnosed and treated for neuroendocrine tumors were investigated. RESULTS: Of the total, 30 (58%) were females and 22 (42%) were males. The localization of the disease was gastroenteropancreatic in 29 (56%) patients and other sites in 23 (44%). The most frequently involved organ in the gastroenteropancreatic system was the stomach (n=10, 19%) and the most frequently involved organ in other regions was the lungs (n=10, 19%). No correlation was found between immunohistochemical staining for proteins such as chromogranin A, synaptophysin, and NSE and the grade of the tumor. The patients were followed-up at a median of 24 months (1-90 months). The three-year overall survival rate was 71%: 100% in stage I, 88% in stage II, 80% in stage III, and 40% in stage IV. The three-year survival rate was 78% in tumors localized in the gastroenteropancreatic region, and 54% in tumors localized in other organs. In the univariate analysis, gender, age, performance status of the patients, grade, localization, surgical treatment, and neutrophil/ lymphocyte ratio (≤ 5 versus >5) affected the prognosis of the patients. CONCLUSIONS: Most of the tumors were localized in the gastroenteropancreatic region, and the three-year survival rate in tumors localized in this region was better than the tumors localized in other sites. Surgical treatment was a positive independent prognostic factor, whereas Grade 3 and a neutrophil/lymphocyte ratio of >5 were negative independent prognostic factors.