Who would be the winner? A prognostic nomogram for predicting the benefit of postoperative radiotherapy ± chemotherapy in patients with locally advanced gastric cancer: TROD-02-01 study.

OBJECTIVES: We aimed to develop a basic, easily applicable nomogram to improve the survival prediction of the patients with stage II/III gastric cancer (GC) and to select the best candidate for postoperative radiotherapy (RT). METHODS: In this multicentric trial, we retrospectively evaluated the data of 1597 patients with stage II/III GC after curative gastrectomy followed by postoperative RT ± chemotherapy (CT). Patients were divided into a training set (n = 1307) and an external validation set (n = 290). Nomograms were created based on independent predictors identified by Cox regression analysis in the training set. The consistency index (C-index) and the calibration curve were used to evaluate the discriminative ability and accuracy of the nomogram. A nomogram was created based on the predictive model and the identified prognostic factors to predict 5-year cancer-specific survival (CSS) and progression-free survival (PFS). RESULTS: The multivariate Cox model recognized lymph node (LN) involvement status, lymphatic dissection (LD) width, and metastatic LN ratio as covariates associated with CSS. Depth of invasion, LN involvement status, LD width, metastatic LN ratio, and lymphovascular invasion were the factors associated with PFS. Calibration of the nomogram predicted both CSS and PFS corresponding closely with the actual results. In our validation set, discrimination was good (C-index, 0.76), and the predicted survival was within a 10% margin of ideal nomogram. CONCLUSIONS: In our relatively large cohort, we created and validated both CSS and PFS nomograms that could be useful for underdeveloped or developing countries rather than Korea and Japan, where the D2 gastrectomy is routinely performed. This could serve as a true map for oncologists who must make decisions without an experienced surgeon and a multidisciplinary tumor board.

A dosimetric comparison for SBRT plans of localized prostate cancer between Cyberknife and Varian Truebeam STX device.

As the Stereotactic Body Radiotherapy (SBRT) approach began to increase in treating patients with localized prostate cancer, it became necessary to investigate which methods used in practice were better. The aim of this study is to perform a dosimetric comparison of the advantages and disadvantages of SBRT treatments for localized prostate cancer delivered by CyberKnife (CK) and Varian Truebeam STX (FF and FFF). Seventeen intermediate and high-risk patients with localized prostate cancer were included in the study. SBRT plans for the CK system and Varian Truebeam STX systems with and without Flattening Filters (Tru-FF and Tru-FFF) were prepared for each patient. Plans prepared for each patient were planned at a fraction dose of 6.7 Gy at 6 MV energy and a target dose of 33.5 Gy in 5 fractions. For all plans, cumulative dose-volume histograms (DVHs) were generated for target volumes and organs at risk (OAR). The maximum doses of PTV (41 Gy) in CK plans are higher than the maximum doses (35 Gy) in VMAT plans prepared with Tru-FF or Tru-FFF beams. The mean dose of the rectal wall (10.06 ± 2.40Gy for CK) is still relatively low compared to other plans (13.46 ± 2.16 Gy for Tru-FF and 13.61 ± 2.32 Gy for Tru-FFF). The bladder wall (14 Gy for CK, 26 Gy for Tru-FF and Tru-FFF) and femoral head (6.8 Gy for CK, 9 Gy for Tru-FF and 9.4 Gy Tru-FFF) doses were also lower for CK plans. The CK plans provide better tumour control due to low doses in critical organs and high target doses than the Tru-FF or Tru-FFF plans. It was observed that CK and VMAT plans for SBRT with 6 MV photon beams provided acceptable results in term of treatment planning criteria such as Conformity Index and Homogeneity Index. It is recommended to use a target tracking system to provide an accurate and reliable SBRT treatment with VMAT and CK techniques.

Evaluation of Nutritional Status and Anxiety Levels in Patients Applying to the Radiation Oncology Outpatient Clinic during the COVID-19 Pandemic: Turkish Society for Radiation Oncology Group Study (TROD 12:02).

Cancer patients often face malnutrition, which negatively affects their response to cancer treatment. This study aims to analyze the effects of the COVID-19 pandemic on nutritional status and anxiety in cancer patients with different types and stages of cancer. This is a cross-sectional cohort study that includes 1,252 patients with varying cancer types from 17 radiation oncology centers. The nutritional risk scores (NRS-2002) and coronavirus anxiety scale (CAS) scores of all patients were measured. NRS-2002 ≥ 3 and CAS ≥ 5 were accepted as values at risk. Of all patients, 15.3% had NRS-2002 ≥ 3. Breast cancer was the most prevalent cancer type (24.5%) with the lowest risk of nutrition (4.9%, p < 0.001). Nutritional risk was significantly higher in patients with gastrointestinal cancer, head and neck cancer, and lung cancer (p < 0.005) and in patients with stage IV disease (p < 0.001). High anxiety levels (CAS ≥ 5) were significantly related to voluntary avoidance and clinical postponement of hospital visits due to the pandemic (p < 0.001), while clinical postponement was particularly frequent among patients with NRS-2002 < 3 (p = 0.0021). Fear and anxiety in cancer patients with COVID-19 cause hesitations in visiting hospitals, leading to disrupted primary and nutritional treatments. Thus, nutritional monitoring and treatment monitoring of cancer patients are crucial during and after radiotherapy.

Definitive Chemoradiotherapy Results in Synchronous Oligometastatic Non-small Cell Lung Cancer Patients: Turkish Society for Radiation Oncology Group Study (TROD 10-003).

OBJECTIVE: It is aimed to investigate the survival outcomes and prognostic factors after curative treatment of patients diagnosed with synchronous oligometastatic non-small cell lung carcinoma. MATERIALS AND METHODS: Fifty-two patients from 3 centers diagnosed between 2014 and 2019 were analyzed. The treatment results of thoracic and oligometastatic regions were retrospectively evaluated. The Kaplan-Meier method was used to determine the overall survival (OS) and progression-free survival (PFS) and log-rank tests for the factors affecting survival. Cox regression analysis was employed for multivariate analysis. RESULTS: Of the 52 patients, 46 (88%) had <2 organ involvement at diagnosis. Treatment of oligometastasis was radiotherapy (RT) in 37, surgery in 4, and surgery with RT in 11 patients. Median 60 Gy were administered to the thoracic tumor. Median RT dose for oligometastasis was 30 Gy in median 5 fractions with either stereotactic body radiation therapy or conventional RT. The median follow-up was 18 months. The median OS and PFS were 35 and 20 months, respectively. The 1-, 2-, and 3-year OS rates were 80.5%, 60.2%, and 41.2%, while the corresponding PFS rates were 75%, 42.5%, and 21.5%, respectively. Multivariate Cox regression analysis revealed that the Eastern Cooperative Oncology Group performance status of "0" and thoracic RT dose over 60 Gy were significant prognostic factors for both the OS and PFS. CONCLUSIONS: Definitive chemoradiotherapy to the thoracic tumor and treatment of oligometastasis region indicate promising survival outcomes.

Outcomes of thymoma after multimodal therapy and determinants of survival: A 16-year experience of a tertiary cancer center.

BACKGROUND: In this study, we aimed to evaluate the factors that contribute to survival outcomes in patients with thymoma treated with multimodal approaches. METHODS: A total of 203 patients (105 males, 98 females; median age: 49 years; range, 17 to 77 years) with Masaoka-Koga Stage II-IV thymoma between January 2002 and December 2018 were retrospectively analyzed. Data including diagnosis of myasthenia gravis, diagnosis of diabetes mellitus, disease stage, histological type of tumor, capsule invasion and surgical margin status, lymphadenectomy, adjuvant radiotherapy or chemotherapy, time from surgery to the first day of adjuvant treatment, length of hospital stay, and overall and disease-free survival rates were recorded. RESULTS: Of the patients, 91 had Stage II, 67 had Stage III, and 45 had Stage IV disease. A total of 123 patients (61%) had myasthenia gravis. Seventy-six patients received adjuvant radiotherapy and 48 patients received either neoadjuvant (n=35) or adjuvant (n=25) chemotherapy. Higher disease stage, presence of R1 resection, and treatment with chemotherapy were significant factors for decreased disease-free survival time. Older age, higher disease stage, longer postoperative hospital stay, chemotherapy, and disease recurrence were effective contributors to decreased overall survival time. Adjuvant radiotherapy had a statistically significant positive effect on overall survival only in patients with completely resected Stage IV disease (five-year overall survival: 94.7% vs. 79.1%, respectively; p=0.015). In the multivariate analysis, older age (hazard ratio: 4.26), higher disease stage (hazard ratio: 2.95), and longer hospitalization time (hazard ratio: 3.81) were significant prognostic factors for overall survival. Patients with local recurrence who underwent complete resection had a survival time comparable to non-recurrent patients (p=0.753). CONCLUSION: For patients with thymoma, higher disease stage, age ≥50 years, longer hospitalization, and need for chemotherapy are associated with worse survival rates. Adjuvant chemotherapy has a positive impact on Stage IV disease. Resection of recurrent lesions has a valuable impact on survival.

Prognostic factors in medically inoperable early stage lung cancer patients treated with stereotactic ablative radiation therapy (SABR): Turkish Radiation Oncology Society Multicentric Study.

OBJECTIVE: We identified factors influencing outcomes in patients with medically inoperable early stage lung cancer (MIESLC) treated with stereotactic ablative radiation therapy (SABR) at 14 centers in Turkey. MATERIALS AND METHODS: We retrospectively analyzed 431 patients with stage I-II MIESLC treated with SABR from 2009 through 2017. Age; sex; performance score; imaging technique; tumor histology and size; disease stage radiation dose, fraction and biologically effective dose with an α/ß ratio of 10 (BED10 ); tumor location and treatment center were evaluated for associations with overall survival (OS), local control (LC) and toxicity. RESULTS: Median follow-up time was 27 months (range 1-115); median SABR dose was 54 Gy (range 30-70) given in a median three fractions (range 1-10); median BED10 was 151 Gy (range 48-180). Tumors were peripheral in 285 patients (66.1%), central in 69 (16%) and <1 cm from mediastinal structures in 77 (17.9%). Response was evaluated with PET/CT in most cases at a median 3 months after SABR. Response rates were: 48% complete, 36.7% partial, 7.9% stable and 7.4% progression. LC rates were 97.1% at 1 year, 92.6% at 2 years and 91.2% at 3 years; corresponding OS rates were 92.6%, 80.6% and 72.7%. On multivariate analysis, BED10 > 100 Gy (P = .011), adenocarcinoma (P = .025) and complete response on first evaluation (P = .007) predicted favorable LC. BED10 > 120 Gy (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.1-3.2, P = .019) and tumor size (<2 cm HR 1.9, 95% CI 1.3-3, P = .003) predicted favorable OS. No grade 4-5 acute side effects were observed; late effects were grade ≤3 pneumonitis (18 [4.2%]), chest wall pain (11 [2.5%]) and rib fracture (1 [0.2%]). CONCLUSION: SABR produced encouraging results, with satisfactory LC and OS and minimal toxicity. BED10 > 120 Gy was needed for better LC and OS for large, non-adenocarcinoma tumors.

Prognostic significance of early complete response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy: Multicentric study of Turkish Society for Radiation Oncology Group (TROD).

BACKGROUND/AIMS: To assess the effect of various parameters on the oncologic outcomes, including the time interval between therapy and surgery (S) in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: The data of 914 LARC patients who received preoperative CRT between 1994 and 2015 were collected retrospectively. Patients received 45-50.4 Gy RT with 5FU based chemotherapy (CT). They all underwent radical resection followed by maintenance CT. Clinical and pathologic variables were compared between the pCR and no-pCR groups. Survival was estimated by the Kaplan-Meier method and Cox proportional hazard model was used in multivariate analysis. RESULTS: After median follow-up of 60.5 (range=12-297.6) months, median overall survival (OS) was 58.75 months and disease-free survival (DFS) 53.32 months. pCR was observed in 18.9% of all cases. pCR, lymphovascular invasion and metastatic lymph node ratio (mLNR) were significantly associated with OS and DFS on multivariate analysis. The 5-year OS and DFS rates were better in pCR group (95.3% vs 80.7% for OS, p<0.0001 and 87.4% vs 71% for DFS, p<0.0001). pCR patients with 4-8 weeks interval had lower rates of distant metastasis (9% vs 20%, p=0.01) and any recurrences (13.6% vs 29.6%, p=0.001) than the remaining. Both OS and DFS were better in favor of pCR achieved at 4-8 week interval time (p<0.0001 for each). CONCLUSION: pCR after preoperative CRT in LARC correlated with better oncologic outcome. The best OS and DFS durations were achieved in patients who experienced pCR after 4-8-weeks interval before surgery.

The Impact of Primary Tumor and Locoregional Metastatic Lymph Node SUVmax on Predicting Survival in Patients with Rectal Cancer.

OBJECTIVES: The aim of this study was to evaluate the impact of maximum standard uptake value (SUVmax) of the primary tumor and locoregional metastatic lymph node in predicting survival in patients with the preoperative rectal adenocarcinoma. METHODS: One hundred and fifteen patients [mean age ± standard deviation (SD): 58.7±11.4 years] with biopsy-proven rectal adenocarcinoma underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging for the staging were included in this study. All patients were followed-up for a minimum of 12 months (mean ± SD: 29.7±13.5 months). Tumor-node-metastasis 2017 clinical staging, SUVmax of the primary rectal tumor and locoregional lymph nodes on the PET/CT studies were evaluated. RESULTS: All patients had increased FDG activity of the primary tumor. The mean ± SD SUVmax of the primary tumor and locoregional metastatic lymph node were 21.0±9.1 and 4.6±2.8, respectively. Primary tumor SUVmax did not have an effect on predicting survival (p=0.525) however locoregional metastatic lymph node SUVmax had an effect (p<0.05) on predicting survival. Clinical stage of the disease was a factor predicting survival (p<0.001). CONCLUSION: 18F-FDG PET/CT is an effective imaging modality for detecting primary tumors and metastases in rectal adenocarcinoma and clinical stage assessment with PET/CT had an effect on predicting survival. Furthermore, in our study locoregional lymph node SUVmax was defined as a factor in predicting survival.

Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase II study.

AIM: To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy (HART) and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS: A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil (325 mg/m2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS: In the early phase of treatment, 6 patients had grade III-IV gastrointestinal toxicity, 2 patients had grade III-IV hematologic toxicity, and 1 patient had grade V toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade IV tenesmus. Complete pathological response was achieved in 6 patients (21%), while near-complete pathological response was obtained in 9 (31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively. CONCLUSION: Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.

Association of Three Single Nucleotide Polymorphisms in MTR and MTRR Genes with Lung Cancer in a Turkish Population.

AIMS: Folate metabolism plays a critical role in DNA methylation and synthesis. Polymorphisms in folate metabolism may affect enzyme activities and thereby affect the cancer risk. Methionine synthase (MTR) and methionine synthase reductase (MTRR) are critical enzymes for the folate cycle. In this study, possible associations between genetic variabilities in MTR and MTRR and susceptibility to lung cancer (LC) were investigated in a Turkish population. METHODS: A case-control study with 193 LC cases and 199 noncancerous controls was conducted. DNA was extracted from leukocytes using the high pure polymerase chain reaction (PCR) template preparation kit. The MTR 2756 A>G (rs1805087), MTRR 524 C > T (rs1532268), and MTRR 66 A>G (rs1801394) genotypes were determined using PCR-restriction fragment length polymorphism (PCR-RFLP) assays. The genotype and haplotype analyses of these polymorphisms were performed using SPSS 21 and Haploview 4.2, respectively. RESULTS: An association between the MTRR A66G polymorphism and LC (p = 0.042) was found. In addition, this allele was observed more frequently in smokers compared to nonsmokers (p = 0.030). In contrast, the distribution of the MTR 2756 A>G and the MTRR 524 C > T allele frequencies were similar in the subject cases and controls. CONCLUSIONS: In conclusion, the present study suggests an association between the MTRR 66 A>G gene polymorphisms and LC risk in a Turkish population.

Delayed versus immediate surgery following short-course neoadjuvant radiotherapy in resectable (T3N0/N+) rectal cancer.

PURPOSE: Preoperative short-course radiotherapy (SCRT) followed by surgery has shown advantage over surgery alone in patients with resectable rectal carcinoma (RC); however, the importance of the timing of surgery after SCRT has not been well defined. This study aimed to investigate the effect of this duration on treatment outcomes. METHODS: Patients who underwent surgery after SCRT (25 Gy/500 cGy/daily/5fr, monday-friday) for resectable and infraperitoneal rectal adenocarcinoma (T3N0/(+)) were included into the study. Patients were divided into two groups in terms of the timing of surgery: delayed surgery (>4 weeks) or immediate surgery (<4 weeks). RESULTS: A hundred and thirty-six patients were included in the study. Median time between RT and surgery was 4 ± 5.7 (1-58) weeks, where 68% (n = 93) patients underwent delayed surgery (≥4 weeks). The two groups did not differ in terms of surgical margin positivity, pathological tumor regression, N downstaging, or T downstaging (p > 0.05 for all). However, the number of positive lymph nodes was higher in the immediate surgery group [median 3 (0-18) vs. 1 (0-17), p = 0.009]. Median follow-up time was 36 ± 9 (6-93) months. Delayed surgery group had significantly longer mean overall survival (p = 0.038); however, the two groups did not differ in terms of local recurrence, mean time to local recurrence, or mean disease-free survival. CONCLUSIONS: Our findings seem to support the benefit of a longer time interval between radiotherapy and surgery after short-course neoadjuvant radiotherapy in resectable rectal cancer in terms of overall survival. However, there is a need to better define patient characteristics that might benefit from delayed surgery.

Chronomodulated oxaliplatin plus Capecitabine (XELOX) as a first line chemotherapy in metastatic colorectal cancer: A Phase II Brunch regimen study.

PURPOSE: The aim of this study was to evaluate safety and toxicity of chronomodulated capecitabine administered in the morning and at noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first-line XELOX chemotherapy in patients with metastatic colorectal cancer. METHODS: A total of 30 treatment-naïve colorectal cancer patients with metastatic disease were included. Oxaliplatin 130 mg/m(2) on day 1 plus chronomodulated oral capecitabine 2000 mg/m(2) per day were administered (50 % dose at 8:00 a.m. and 50 % dose at 12:00 noon on days 1-14, every 21 days). All adverse events, treatment responses and survival were evaluated. In addition, pharmacokinetic profile of capecitabine was examined in a subset of 5 patients. RESULTS: Median age was 57.1 years (range 32-77 years). Median follow-up was 19 months (range 3-36 months). Three patients (10 %) had complete response, 13 patients (43.3 %) had partial response and 4 patients (13.3 %) had stabile disease. Ten patients had progressive disease at their first evaluation (33.3 %). The median progression-free survival (PFS) was 10 months (range 2-36 months). There were no grade 4 toxicities. One patient (3.3 %) had grade 3 neutropenia. Hand-foot syndrome developed in three patients (10 %): 6.6 %, grade 1 and 3.3 %, grade 2. CONCLUSIONS: Chronomodulated XELOX seems to represent a promising therapeutic option in the first-line treatment of metastatic colorectal carcinoma due to good tumor control and favorable toxicity profile. Phase III randomized trials are required to assess the actual clinical efficacy and side effect profile of this regimen.

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

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

Adjuvant chemoradiotherapy after D2 resection in gastric cancer: a single-center observational study.

PURPOSE: Previous studies demonstrated survival benefits in association with the addition of chemoradiotherapy after surgery in gastric cancer. This study aimed to examine the efficacy in terms of loco-regional control and survival and safety of 5-FU-based adjuvant chemoradiotherapy after D2 curative surgery. METHODS: This study included 228 patients (81 female, 147 male) treated for gastric cancer with curative surgery plus adjuvant chemoradiotherapy. Majority of the patients underwent at least D2 lymph node resection. Median three cycles of fluorouracil chemotherapy were administered, and 45-Gy radiotherapy was delivered at 1.8 Gy/fraction concomitantly during the second cycle of chemotherapy. Local control, regional control, distant metastasis and overall survival rates were estimated. RESULTS: The median age of the patients was 54 years (range 25-74 years). The most common grade III toxicities were nausea (10%) and neutropenia (9%). During radiotherapy, grade IV local skin reaction occurred in one patient. Median duration of follow-up was 47 months. Local, regional and distant recurrence developed in 9 (4%), 41 (18%) and 45 (20%) patients, respectively. Overall 5-year survival rate was 57.2%, and disease-free 5-year survival rate was 53.8%. Multivariate analysis identified less than 15 lymph node involvement as an independent predictor of better survival (p < 0.001). CONCLUSIONS: Concomitant 5-FU-based chemoradiotherapy seems to be an effective and tolerable adjuvant regimen on local control and survival in curatively resected node-positive stomach cancer, particularly when combined with D2 resection.

Does Metastatic Lymph Node SUVmax Predict Survival in Patients with Esophageal Cancer?

OBJECTIVE: We aimed to investigate the SUVmax of primary tumor and metastatic lymph node in predicting survival in patients with esophageal cancer. METHODS: We retrospectively analyzed patients with esophageal cancer between 2009 and 2011 who had FDG positron-emission tomography (PET)/computed tomography (CT). All patients were followed-up to 2013. Clinical staging, SUVmax of primary tumor and metastatic lymph node were evaluated. RESULTS: One hundred seven patients were included in the study. All patients were followed-up between 2 and 49 months. The mean SUVmax of primary tumor and metastatic lymph node were 19.3±8.8 and 10.4±9.1, respectively. Metastatic lymph node SUVmax had an effect in predicting survival whereas primary tumor SUVmax did not have an effect (p=0.014 and p=0.262, respectively). Multivariate Cox regression analysis showed that clinical stage of the disease was the only independent factor predicting survival (p=0.001). CONCLUSION: Among patients with esophageal cancer, the value of primary tumor SUVmax did not have an effect on survival. Clinical stage assessed with FDG PET/CT imaging was found to predict survival in esophageal carcinoma. Additionally, lymph node SUVmax was identified as a new parameter in predicting survival in the present study.

The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG).

Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5-92), and the mean survival was 25.8 months (95 % CI 20.4-29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27-4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities.

Neoadjuvant chronomodulated capecitabine with radiotherapy in rectal cancer: a phase II brunch regimen study.

PURPOSE: The aim of this study was to evaluate efficacy and safety of chronomodulated capecitabine administered according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer. METHODS: Eighty-five patients with stage II and III rectal cancer were included. Patients received capecitabine (1,650 mg/m(2) per day; 60% dose at 8:00 AM and 40% dose at 12:00 noon) administered during pelvic radiation (total 50.4 Gy in 28 fractions, 1.8 Gy daily dose between 2:00 p.m. and 4:00 p.m.). After chemoradiotherapy, patients underwent surgery. The primary endpoints were pathological complete response (pCR) rate and toxicity. RESULTS: In 17 patients (20%), total tumor regression was achieved according to Dworak pathological grading system. Grade III diarrhea occurred in nine patients (10.5%), while only one patient had grade 3 thrombocytopenia. Grade II or III proctitis were seen in nine (10.5%) subjects, and grade I or II cystitis in six (6.9%). Only three patients (3.3%) developed hand and foot syndrome (both grade I-II). There were no grade IV toxicities. CONCLUSIONS: Brunch Regimen for locally advanced rectal cancer consisting of neoadjuvant chronomodulated capecitabine and concurrent radiation therapy is effective and well tolerated with good safety profile, particularly with regard to the occurrence of hand and foot syndrome, in patients with locally advanced rectal cancer.

Do CDKN2 p16 540 C>G, CDKN2 p16 580 C>T, and MDM2 SNP309 T>G gene variants act on colorectal cancer development or progression?

CDNK2 p16 plays a pivotal role in G1/S transition by regulating the p53 pathway, which was regulated by a nuclear oncoprotein, mouse double minute 2 (MDM2). Overexpression of the MDM2 gene has been shown in a number of tumor types, its gene amplification is found to associate with accelerated tumor development and failure to treatment in both hereditary and sporadic cancers. Although genetic association studies have revealed the relationship between certain genetic polymorphisms and genes that play important roles in the development and progression of colorectal cancer (CRC), it is still unknown. Therefore, the polymorphisms of p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G designed to investigate the risk of CRC development and progression in a Turkish population. We enrolled 87 patients with CRC and 75 healthy controls into the study. Genotypings were determined using polymerase chain reaction-restriction fragment length polymorphism techniques. Genotype distributions of p16 540 C>G and 580 C>T were found in agreement with the Hardy-Weinberg equilibrium in patients and controls. MDM2 SNP309 T>G was found in agreement with the Hardy-Weinberg equilibrium in controls, but not in patients. The results of our study, the G allele of p16 540 C>G and GG genotype of MDM2 SNP309 T>G were found significantly lower in patients compared with controls (p<0.001, p<0.05, respectively). Haplotype analyses have shown that the C allele of both the CDKN2 p16 540 C>G and 580 C>T variants together indicate a risk haplotype for the patient group; besides, carrying the G allele of p16 540 and G allele of MDM2 also seems a risk haplotype for the patient group. Our study is the first study that investigates the relationship among variants of CDKN2 p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G risk of CRC and the development and progression in the Turkish population.

Paraoxonase-1 192/55 polymorphisms and the risk of lung cancer in a Turkish population.

AIM: The purpose of the present study was to investigate the possible association of paraoxonase-1 (PON1) 192/55 polymorphisms with lung cancer (LC) risk in a Turkish population. MATERIALS AND METHODS: A population-based, case-control study was carried out, including 223 patients with LC and 234 controls. The frequencies of PON1 192/55 genotypes were compared in patient and control groups using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Distribution of PON1 192 R (+) genotype was found to be significantly higher in patients with LC compared to the controls (odds ratio: 1.497, 95% confidence interval: 1.034-2.166). This difference was especially noteworthy in patients with small cell carcinoma and squamous cell carcinoma. CONCLUSION: This is the first case-control study on the association between PON1 polymorphisms and LC susceptibility in a Turkish population. Our results suggest that PON1 192 polymorphsim is associated with an increased risk of LC in the Turkish population and may be a useful genetic marker for small cell and squamous cell carcinoma.