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 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 characteristics and risk factors for common psychiatric disorders in patients with cancer seeking help for mental health.

BACKGROUND: Although the adverse effects of cancer diagnoses and treatments on mental health are known, about less than 10% of patients are estimated to be referred to seek help. The primary purpose of this study was to obtain the baseline information on patients with cancer seeking help for mental health who presented for the first time to the psycho-oncology outpatient clinic, and to identify risk factors that may provide clues healthcare practitioners in recognizing those needing psychological help in oncology practice. METHODS: We reviewed the charts of 566 patients with cancer who were referred to the psycho-oncology outpatient clinic over a two-year period. The study includes the socio-demographic data, illness characteristics, psychiatric characteristics, psychiatric diagnoses, and treatment recommendations for these patients. RESULTS: The incidence of diagnoses of psychiatric disorders was 97.5%. The distributions of psychiatric diagnoses were as follows: any kind of adjustment disorders, mood disorders, anxiety disorders, organic brain syndrome, personality disorders, delusional disorder, and insomnia. Recurrence of cancer, other chronic medical illnesses, a history of psychiatric disorders, poor social support, and low income comprised the common significant risk factors for adjustment disorders, mood disorders, and anxiety disorders. These risk factors were also seen to be significant in the regression analysis in terms of sex. CONCLUSION: This study identifies the distribution of psychiatric disorders, the risk factors for specific psychiatric disorders, and draws attention to the fact that there are serious delays in patients seeking psychiatric help and in the referrals of oncologists for psychological assessment. Identifying risk factors and raising oncologists' awareness toward risk factors could help more patients gain access to mental health care much earlier.

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.

Neoadjuvant volumetric modulated arc therapy in rectal cancer and the correlation of pathological response with diffusion-weighted MRI and apoptotic markers.

PURPOSE: In this prospective observational study, we aimed to report the applicability and tolerability of neoadjuvant volumetric modulated arc therapy with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in patients with locally advanced rectal cancer (LARC), and to evaluate the correlation of pathological response with apparent diffusion coefficient (ADC) measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and apoptotic markers. METHODS: The study enrolled 30 patients with T3 to T4 and/or N+ rectal cancer who preoperatively received SIB-VMAT and concurrent chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers including the nucleosomes and cell-free DNA fragments in the serum samples were examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC measurements on the DW-MRI were analyzed. RESULTS: No patients had acute or chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in 8 patients (27%), while in 10 patients (33%) near-complete pathological response was obtained. Posttreatment ADC was significantly higher in patients with pCR compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3% for distinguishing the patients with pCR from other responders. On the other hand, posttreatment DNA integrity values were revealed lower than the pretreatment values (p = 0.36). Also, the results revealed an insignificant increase in the posttreatment serum level of nucleosomes (p = 0.72). CONCLUSIONS: Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible treatment regimen in LARC with tolerable side effects, and improved local control rate and pCR rate.

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.

Factors affecting progression-free survival in non-HIV-related Kaposi sarcoma.

BACKGROUND: Non-HIV related Kaposi sarcoma (NHKS) is a rare indolent neoplasm which is more common around Mediterranean origin. Data concerning factors that influence progression-free survival (PFS) for NHKS are insufficient. The purpose of present retrospective analysis was to distinguish the factors affecting PFS in patients with NHKS. METHODS: A hundred and twenty-eight consecutive patients with NHKS who were treated or observed between 1997 and 2014 at Istanbul University Institute of Oncology were included into the study. Treatment response and progression definitions were determined according to different treatment modalities administered at first line. RESULTS: Majority of patients were male (n = 97, 75.8%). Median age of the whole group was 66 years (28-85). Of the patients, 15 patients were immunosuppressant, whereas 113 patients had no disease that caused immunosuppression. Patients were treated with local excision (n = 57, 44.5%), chemotherapy (n = 32, 25.0%) and/or radiotherapy (n = 13, 10.2%) or observed without treatment (n = 26, 20.3%). At a median follow-up of 28 months, 71 (55.5%) patients had progression, while 3 patients (2.3%) died of NHKS. On univariate analysis, patients who had hypertension (HT) had poorer PFS compared with others (19 ± 12 versus 41 ± 22 months; p = 0.03), whereas plaque formation was associated with better outcome (25 ± 9 versus 54 ± 12 months; p = 0.03). In addition, heavy smoking (≥40 pack-years) had a borderline significance regarding better PFS time (23 ± 24 versus 45 ± 38 months, p = 0.06). On multivariate analysis, none of factors evaluated had any impact on PFS. CONCLUSIONS: HT was correlated with poorer outcome among NHKS patients. Patients with plaque formation and ≥40 pack-years of smoking had better PFS than others.

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.

Fourth versus eighth week surgery after neoadjuvant radiochemotherapy in T3-4/N0+ rectal cancer: Istanbul R-01 study.

BACKGROUND AND PURPOSE: The optimum duration between neoadjuvant radiochemotherapy and transmesorectal excision in locally advanced rectal cancer has not been defined yet. This randomized study was designed to compare the efficacy of four-week versus eight-week delay before surgery. METHODS: One-hundred and fifty-three patients with locally advanced low- or mid-rectum rectal adenocarcinoma were included in this single center prospective randomized trial. Patients were assigned to receive surgical treatment after either four weeks or eight weeks of delay after chemoradiotherapy. Patients were followed for local recurrence and survival, and surgical specimens were examined for pathological staging and circumferential margin positivity. RESULTS: 4-week and 8-week groups did not differ with regard to lateral surgical margin positivity (9.2% vs. 5.1%, P=0.33, respectively), pathological tumor regression rate (P=0.90), overall survival (5-year, 76.5% vs. 74.2%, P=0.60) and local recurrence rate (11.8% vs. 10.3%, 0.77). Overall survival was better in patients with negative surgical margins (78.8% vs. 53.0%, P=0.04). Local recurrence rate was significantly higher among patients with positive surgical margin (28.5% vs. 9.3%, P=0.02). CONCLUSIONS: Intentional prolongation of the chemoradiotherapy-surgery interval does not seem to improve clinical outcomes of patients with locally advanced rectal cancer. Surgical margin positivity seems to be more important with this regard.

Comparison of two different adjuvant treatment modalities for pN3 gastric cancer patients after D2 lymph node dissection: can we avoid radiotherapy in a subgroup of patients?

Adjuvant chemoradiotherapy (CRT) is the standard of care for gastric cancer patients in the USA. However, in countries where D2 lymph node dissection is performed, the effect of radiotherapy on locoregional recurrence is controversial. The aim of this study is to compare the outcomes in pN3 gastric cancer patients following two adjuvant treatment modalities: chemotherapy (CT) and CRT after D2 lymph node dissection. Between 2005 and 2009, 71 gastric cancer patients who underwent D2 lymph node dissection and had pTanyN3M0 stage (according to AJCC 6th edition) were identified. Fifty-three patients were treated with CT and 18 patients received CRT. CRT consisted of bolus fluorouracil (FU) 425 mg/m(2) and leucovorin 20 mg/m(2) before, after, and during radiotherapy. For the CT arm, treatment protocols consisted of combination therapies involving FU and cisplatin as the backbone. Median overall survival (OS) and disease-free survival (DFS) rates for all patients were 26.3 months (15-37.7 months) and 12.5 months (8-17.1 months). Median OS in CT arm was 26.8 months and it was 34.2 months for CRT arm (p = 0.74). DFS rates did not differ statistically either (p = 0.56, 12.5 and 15.2 months for CT and CRT, respectively). Locoregional recurrence rates were also similar (p = 0.63). Only metastatic/dissected lymph node ratio (≥0.75) was identified as a prognostic factor in both univariate and multivariate analyses for DFS. Comparison of CT versus CRT for N3 stage gastric cancer patients with D2 lymph node dissection did not reveal any statistically significant difference in survival rates and locoregional recurrence.

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.

Weekly docetaxel and cisplatin with concomitant radiotherapy in addition to surgery and/or consolidation chemotherapy in stage III non-small cell lung cancer.

PURPOSE: The aim of this study was to evaluate efficacy and feasibility of a combination of weekly docetaxel and cisplatin administered concomitantly with radiotherapy followed by surgery in addition to consolidation chemotherapy with docetaxel and cisplatin administered every 3 weeks in stage III non-small cell lung cancer (NSCLC). METHODS: A total of 31 histologically proven, locally advanced (stage IIIA-N2 = 9, stage IIIB-T4N0-2 = 22) NSCLC patients were investigated. After administration of 4-6 cycles of weekly docetaxel (20 mg/m(2)) and weekly cisplatin (20 mg/m(2)) concurrently with radiotherapy, patients underwent operation if their disease was appropriately downstaged. Combination chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks was administered as a consolidation regimen. The treatment response, toxicity, time to progression (TTP) and overall survival (OS) were evaluated. RESULTS: After concomitant chemoradiotherapy, complete response and partial response occurred in 16.1 and 67.7% of patients, respectively. Thirteen percentage of patients progressed on treatment, and 3.2% had stable disease. Grade 3-4 hematologic and skin toxicities did not occur, whereas 17.9% of them experienced grade 3-4 oesophageal toxicity. Grade 3 pulmonary toxicity and grade 3-4 emesis developed in 9.7 and 6.4% of patients, respectively. Thirteen responsive patients (41.9%) underwent surgery. The toxicity of consolidation chemotherapy was tolerable. Median OS and TTP were 22 ± 5 (range 13-31) and 12 ± 3 (range 7-17) months, respectively. Median follow-up was 22 (range 2-57) months. CONCLUSIONS: Weekly administration of docetaxel and cisplatin concurrently with radiotherapy followed by consolidation chemotherapy is an effective treatment with acceptable toxicity for patients with locally advanced NSCLC especially in combination with surgery.

Treatment outcome and prognostic factors in non-metastatic esophageal carcinoma.

OBJECTIVE: To investigate the therapeutic outcome and prognostic factors in patients with non-metastatic esophageal carcinoma. METHODS: Between January 1989 and December 2003, 171 patients with non-metastatic esophageal carcinoma patients were retrospectively assessed in the Department of Radiation and Oncology, Institute of Oncology, Turkey. RESULTS: The distribution of the stage at presentation designated 39 stage II patients (23%) and 132 stage III patients (77%). The primary tumors were treated with surgery and postoperative radiotherapy (RT) in 29 patients (17%), with surgery, postoperative RT and chemotherapy (CT) in 17 patients (10%), with radical RT in 40 patients (23%), and with RT and CT in 47 patients (27%). Fourteen patients (8%) did not receive any postoperative adjuvant treatment. Two and three-year survival rates of the whole group were 27.0% and 14.8%, respectively. Clinical staging was the only statistically significant prognostic factor by multivariate analyses (p=0.04). Median survivals by the treatment groups were 12.5 months for surgery alone, 16 months for surgery plus postoperative RT, 15 months in surgery plus postoperative chemoradiotherapy, 9 months in radical RT alone and 17 months in chemoradiotherapy group. Survival advantage was not demonstrated for postoperative RT or RT plus CT. Outcomes were similar between the patients treated with surgery and with chemoradiotherapy (p=0.54). Patients treated with chemoradiotherapy had a longer survival than patients treated with only RT (p=0.05). CONCLUSION: The most important prognostic factor was the stage of the disease. Survival advantage was not demonstrated for postoperative RT or RT plus CT. Outcomes were similar between patients treated by surgery and by chemoradiotherapy.

Resectable thymoma: treatment outcome and prognostic factors in the late adolescent and adult age group.

The aim of this study was to investigate the therapeutic outcome and prognostic factors in 36 patients with resectable thymoma who were referred to our clinic following surgical resection. The median age was 45 years, ranging from 19 to 72 years. Myastenia gravis was observed in 28 patients (77.7%). The most frequent histologic subtype was epithelial (n = 21, 58.3%), followed by the lymphocytic type (n = 6, 16.7%). Stage at presentation was distributed as stage 1, 2 patients (2.7%); stage 2, 19 patients (52.8%); stage 3, 10 (27.8%); and stage 4, 3 patients (8.3%). The majority of the patients (n = 32, 88.9%) had completely resectable disease, whereas 2 patients had microscopic and 2 more patients had macroscopic residual disease after surgery. Adjuvant radiotherapy was administered to 28 patients. After a median follow-up period of 39 months, 5 patients (16.1%) experienced recurrence. There was a significant negative correlation between recurrence and adjuvant radiation therapy (two-sided p = 0.0001). There were no objective responses to chemotherapy given to 4 patients for recurrent disease. Overall survival (OS) and progression-free survival (PFS) was 82.8% and 76.6% at 5 years, respectively. Adjuvant radiotherapy had a significant association with both OS (p = 0.039) and PFS (p = 0.00001). Furthermore, recurrent disease was observed to have a significant negative impact on OS (p = 0.039). The results of this study suggest that adjuvant radiotherapy may provide survival benefit in patients with resectable thymoma, regardless of surgical margins.