Aydin Ciltas

Long Term Survivors with Metastatic Pancreatic Cancer Treated with Gemcitabine Alone or Plus Cisplatin: a Retrospective Analysis of an Anatolian Society of Medical Oncology Multicenter Study

BACKGROUND The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy has limited impact on overall survival (OS) so that eligible patients should be selected carefully. The aim of this study was to analyze prognostic factors for survival in Turkish advanced pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving gemcitabine (Gem) alone or gemcitabine plus cisplatin (GemCis). METHODS This retrospective evaluation was performed for patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and who received gemcitabine between December 2005 and August 2011. Twenty-seven potential prognostic variables were chosen for univariate and multivariate analyses to identify prognostic factors associated with survival. RESULTS Among the 27 variables in univariate analysis, three were identified to have prognostic significance: sex (p=0.04), peritoneal dissemination (p=0.02) and serum creatinine level (p=0.05). Multivariate analysis by Cox proportional hazard model showed only peritoneal dissemination to be an independent prognostic factor for survival. CONCLUSION In conclusion, peritoneal metastasis was identified as an important prognostic factor in metastatic pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/ or metastatic disease and receiving Gem or GemCis. The findings should facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.

Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third‑ or fourth‑line treatment: A retrospective multicenter experience

Sorafenib is a multi-targeted tyrosine kinase receptor inhibitor used to treat patients with advanced gastrointestinal stromal tumors (GISTs). The present study evaluated the efficacy and tolerability of sorafenib therapy for patients with GISTs. Between January 2001 and November 2012, 25 patients, from multiple centers, who had received sorafenib as the third- or fourth-line treatment for GISTs were investigated retrospectively. In total, 17 patients were male and eight were female. The median age was 54.0 years (range, 16–82 years). From the patients, 21 received imatinib for longer than six months and four received it for less than six months. The clinical benefit rate of sorafenib was 40.0%. Treatment-related adverse events were reported in 72% of patients. These adverse events were generally mild to moderate in intensity. The median progression-free survival (PFS) and overall survival (OS) times of the patients who received sorafenib were 7.2 and 15.2 months, respectively. The duration of imatinib usage was an independent prognostic factor for PFS and OS. Sorafenib is an effective treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an acceptable tolerability.

Efficacy and safety of raltitrexed combinations with uracil- tegafur or mitomycin C as salvage treatment in advanced colorectal cancer patients: a multicenter study of Anatolian Society of Medical Oncology (ASMO).

BACKGROUND There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. MATERIALS AND METHODS A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 mg/m2 (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 mg/m2 i.v. on day every 3 weeks (group B). RESULTS Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46). CONCLUSIONS The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.

Evaluation of Prognostic Factors and Adjuvant Chemotherapy in Patients With Small Bowel Adenocarcinoma Who Underwent Curative Resection

Background: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Because these are rarely encountered tumors, the aim of this multicenter study was evaluation of prognostic factors and adjuvant chemotherapy in patients with curatively resected SBA. Materials and Methods: A total of 78 patients diagnosed with curatively resected SBA were involved in the retrospective study. Forty‐eight patients received 1 of 3 different chemotherapy regimens, whereas 30 patients did not receive any adjuvant treatment. No adjuvant and adjuvant chemotherapy cohorts were matched (1:1) by propensity scores based on the likelihood of receiving chemotherapy or the survival hazard from Cox modeling. Overall survival (OS) was compared with Kaplan‐Meier estimates. Results: Median age of 78 patients with curatively resected SBA was 58, and 59% of these were men. According to TNM classification, 8 (10%) of the patients were at stage I, 26 (34%) were at stage II, and 44 (56%) were at stage III. Median follow‐up duration was 29 months. Three‐year median disease‐free survival (DFS) and OS were 62.5% and 67.0%, respectively. In univariate analysis, presence of vascular invasion, perineural invasion, lymph node involvement, and presence of positive surgical margin were significant predictors of poor survival. Multivariate analysis showed that the only adverse prognostic factor independently related with OS was the presence of positive surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.11‐1.26; P = .01). Neither DFS nor OS was found to be significantly improved by the adjuvant chemotherapy in both matched and unmatched cohorts. Conclusions: Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection. &NA; This is a multicenter study to assess the prognostic factors and adjuvant chemotherapy in patients with small bowel adenocarcinoma (SBA). A total of 78 patients with SBA diagnosed with completely resected SBA were involved in the study. Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection. Neither disease‐free survival nor overall survival was found to be significantly improved by the adjuvant chemotherapy

Lobular breast cancer metastasis to uterus during adjuvant tamoxifen treatment: A case report and review of the literature

Tamoxifen plays a critical role in the treatment of hormone receptor-positive breast cancer. Despite these great benefits against breast cancer, tamoxifen increases the risk of endometrial pathologies such as endometrial hyperplasia, polyp, and neoplasms because of agonistic effect on endometrial tissues. Therefore, gynecologic follow-up should be carried out during tamoxifen treatment. Uterine tumors are frequently detected as the result of presentation with abnormal uterine bleeding. In addition, genital tracts metastases from distant primary tumors can present with abnormal uterine bleeding. Therefore, it is important to determine whether the uterine mass is metastatic or primary because different treatment modalities are used for them. In this context, breast carcinomas are the most frequent metastatic tumors, particularly invasive lobular carcinoma. Here, we report an invasive lobular carcinoma case that presented with abnormal uterine bleeding while receiving tamoxifen therapy and has metastasize in the uterus.

A metastatic histiocytic sarcoma case with primary involvement of the tonsil

Histiocytic sarcoma (HS) is an extremely rare and aggressive hematopoietic tumor. Although it can be seen at any anatomic location, the most common primary sites are skin as extranodal region, locations including the lymph nodes and gastrointestinal tract. To the best of our knowledge, in light of PubMed search, this is the first primary tonsillar HS case presented with disseminated metastases at the time of diagnosis. A 58-year-old male patient applied with swelling on the right side of the neck, difficulty in swallowing, and weight loss. Positron emission tomography computed tomography was performed and increased pathological 18F fluorodeoxy D glucose uptake was detected in the right palatine tonsil, bilateral cervical multiple lymph nodes, liver masses, intra abdominal lymph nodes, and nodular lesion in the left adrenal gland. Tonsillectomy was performed and the pathological result was reported as HS. The patient did not respond to any treatment and had died after 5 months from the date of diagnosis. In conclusion, HS is generally diagnosed at advanced stage, it has limited chemotherapy response and high mortality rates. To understand this rare diseases pathophysiological and clinical features, further investigations are needed.

Ewing′s sarcoma of kidney in a 60-year-old patient with local recurrence: A rare occurrence

Ewings family of tumors is aggressive tumors and frequently arises from bone and soft tissue. They might also arise from nonosseous structures such as gastrointestinal tract, adrenal glands, or kidney. Primary renal Ewings sarcoma (ES)/primitive neuroectodermal tumor is an extremely rare entity which has aggressive clinical course. These high-grade malignant tumors predominantly affect adolescents and young adults. Patients mostly present with nonspecific symptoms such as pain, hematuria, mass, and sensitivity. It is confused with renal cell cancer in imaging techniques. The definitive diagnosis is based on the histopathological examination. Surgical or radiotherapy treatment is used for local control and multiagent chemotherapy used for systemic treatment. Despite all treatment options, prognosis is poor. We aimed to describe the diagnosis and follow-up and treatment of renal ES case that was considered as renal cell carcinoma in imaging but diagnosed as ES via histopathology.

A case of membranous glomerulopathy associated with lung cancer and review of the literature

Membraneous nephropathy (MN) is the most commonly occurring nephrotic syndrome in adults as well as the most common paraneoplastic nephropathy associated with solid tumors, and it is mostly associated with gastrointestinal system and lung carcinomas. Accurate diagnosis is important as the treatment of paraneoplastic glomerulonephritis is very varied from that of idiopathic ones. In the current report, a case of a patient that was referred with proteinuria and edema and was diagnosed with lung cancer, and responded markedly to treatment of malignancy, with improvement of MN, is presented. Active cancer is present in all patients with paraneoplastic MN. In numerous patients, the paraneoplastic MN and cancer diagnoses are made within one year of each other. The treatment of paraneoplastic syndromes is usually associated with the treatment of primary malignancy. There are conflicting data on which treatment modality is more suitable. In conclusion, further studies are required in order to determine the actual incidence of cancer in patients with nephropathy, explain the physiopathological association between cancer and nephropathy and to determine the most suitable treatment approaches.

Comparison of survival with somatostatin analog and chemotherapy and prognostic factors for treatment in 165 advanced neuroendocrine tumor patients with Ki-67 20% or less.

The objectives of this study were to compare progression-free survival (PFS) with somatostatin analog (SSA) versus chemotherapy (CTx) in first-line therapy and to determine the patient group in which these treatments were more effective in neuroendocrine tumors (NETs) with a Ki-67 index of 20% or less. Patients who received SSA or CTx and had unresectable locally advanced and metastatic NETs with a Ki-67 index of 20% or less were retrospectively selected from 13 centers in the Turkish database between 2000 and 2015. One hundred and sixty-five patients were enrolled. The median age was 56 years and the male-to-female ratio was 1.09. Seventy-four (45%) patients were of grade 1 NET and 91 (55%) were of grade 2. SSA was given to 104 patients, whereas 61 were treated with CTx. The objective response rate after SSA was 15.4%; another 73.1% had stable disease. The objective response rate after CTx was 36.1%, and 40.9% had stable disease (P=0.008). The median PFS in SSA patients was 21 months (95% confidence interval: 12.4–29.6), and 8 months for CTx (95% confidence interval: 5.5–10.6) (P<0.001). There was no significant difference between PFS of receiving SSA and CTx in pancreatic neuroendocrine tumor (PNET) patients; however, the PFS of receiving SSA was longer in non-PNET patients (P<0.001). SSA was better treatment in advanced NET patients with a Ki-67 index of less than 5%, having a primary resected and a performance status of 0 (P<0.05). SSA may be preferred over CTx in advanced NET patients with low-to-intermediate grade.

Medullary Thyroid Cancer

Medullary thyroid carcinoma (MTC) is an uncommon neuroendocrine tumor (NET) derived from the parafollicular C cells of the thyroid gland. Calcitonin secretion is a universal feature of the tumor. Approximately 25–30 % of the patients present with autosomal dominant hereditary forms as part of multiple endocrine neoplasia (MEN)—MEN-2A, MEN-2B, or familial MTC syndromes. RET proto-oncogene mutations are responsible for the pathogenesis. Hereditary forms are secondary to germline mutations in the RET gene with different penetration rates causing a diversity of disease phenotypes. Majority of the sporadic cases harbor somatic RET gene mutations, whereas about 5 % of those display germline RET gene mutations. Identification of patients genetically at high risk is critical, because affected individuals are best treated with early and prophylactic surgery. Surgical resection remains the principal treatment modality with total thyroidectomy and extended cervical lymph node dissection. Impact of radiotherapy and chemotherapy in the management of MTC is limited, and prognosis of progressive and metastatic disease remains dismal. Improved comprehension of the molecular alterations and discovery of pathways involved in the pathogenesis of MTC have led to the development of specific targeted inhibitors against tyrosine kinases that have changed the way metastatic disease is treated. Vandetanib and cabozantinib are approved by the FDA in the treatment of advanced MTC. Although much progress has been made, there exists an apparent “unmet medical need” for innovative therapeutic approaches in advanced MTC.