Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC.

BACKGROUNDS AND OBJECTIVES: Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS: In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS: A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION: According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

The effect of concomitant use of proton pump inhibitors with CDK 4/6 inhibitors on survival in metastatic breast cancer.

AIM: To evaluate the difference of progression free survival between the patients using concomitant proton pump inhibitors and non-users in the patients using CDK 4/6 inhibitors with HR + and HER2 negative mBC. METHODS: We included 86 patients with HR + and HER 2 negative mBC treated with CDK 4/6 inhibitors in this study. Patients were divided into two categories according to their status of PPI use. The primary end points was progression free survival (PFS). We compared PPI users and non-users. RESULTS: Forty-five (52.3%) patients used a PPI concomitantly with a CDK 4/6 inhibitor, and 41 (47.7%) did not. The median duration of follow-up was 10.68 (1.94-27.56) months. Of the patients, 50 (58.1%) palbociclib and 36 (41.9%) received ribociclib. The median progression free survival (mPFS) was 10.9 months (95% CI: 7.5-14.27) in the group with concomitant PPI use with a CDK 4/6 inhibitor, whereas the median progression free survival could not be reached in the group without concomitant PPI use (p = 0.04). In addition, concomitant PPI use with palbociclib was associated with a shorter PFS; there was no significant difference between the concomitant PPI users and non-users in terms of PFS in the patients using ribociclib. CONCLUSION: Palbociclib and ribociclib are weak base drugs so their bioavailability is pH-dependent. PPIs can affect their solubility and their concentration in the plasma. Therefore, we must avoid concomitant use of PPIs and CDK 4/6 inhibitors. If we need to use concomitant PPI and CDK 4/6 inhibitors, we should prefer ribociclib than palbociclib.

Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

Cisplatin plus paclitaxel and bevacizumab versus carboplatin plus paclitaxel and bevacizumab for the first-line treatment of metastatic or recurrent cervical cancer.

OBJECTIVE: Cisplatin-paclitaxel and bevacizumab is a frequently used treatment regimen for metastatic or recurrent cervical cancer, and carboplatin-paclitaxel and bevacizumab are also among the recommended regimens. In this study we aimed to evaluate the efficacy of these two regimens for the treatment of metastatic or recurrent cervical cancer. METHODS: Patients with metastatic or recurrent cervical cancer treated with cisplatin-paclitaxel and bevacizumab or carboplatin-paclitaxel and bevacizumab were retrospectively evaluated in this study. The clinical and demographic characteristics of patients in each group were evaluated. Median overall survival, progression-free survival, and response rates between the two groups were compared. RESULTS: A total of 250 patients were included. Overall, the numbers of patients with recurrent disease and metastatic disease were 159 and 91, respectively. The most common histologic subtype was squamous cell carcinoma (83.2%). The median duration of follow-up was 13.6 (range 0.5-86) months. The median progression-free survival was 10.5 (95% CI 9.0 to 11.8) months in the cisplatin-paclitaxel and bevacizumab group (group 1), and 10.8 (95% CI 8.6 to 13.0) months in the carboplatin-paclitaxel and bevacizumab group (group 2) (HR 1.20; 95% CI 0.88 to 1.63; p=0.25). The median overall survival was 19.1 (95% CI 13.0 to 25.1) months in group 1 and 18.3 (95% CI 15.3 to 21.3) months in group 2 (HR 1.28; 95% CI 0.91 to 1.80; p=0.15). CONCLUSIONS: There is no survival difference between cisplatin or carboplatin combined with paclitaxel and bevacizumab in metastatic or recurrent cervical cancer.

The Effect of Body Mass Index on Treatment Outcomes in Patients with Metastatic Non-Small Cell Lung Cancer Treated with Platinum-Based Therapy.

To investigate the effect of body mass index(BMI) on treatment outcomes and side-effect profile in metastatic non-small cell lung cancer(NSCLC) patients receiving platinum-based chemotherapy(ChT) in the first-line setting. This was a retrospective analysis of 233 NSCLC patients who were treated and followed up from 2008 through 2018. NSCLC patients who had metastatic disease at the time of diagnosis and were treated with platinum-based ChT in the first-line setting were included. The patients were divided into 2 groups based on the BMI as follows; BMI < 25 kg/m2 and BMI ≥ 25 kg/m2. This retrospective analysis enrolled 233 patients, 35 (15.0%) of whom were female. The BMI in 132 patients (56.2%) was < 25 kg/m2. The median age was 58 years (range, 21-90). Median progression-free survival(PFS) was 7 mo, in the patients with BMI ≥ 25 kg/m2 compared to 5.0 mo, in those with BMI < 25 kg/m2 (p = 0.032), with corresponding median overall survival(OS) durations of 12 vs. 9 mo, (p = 0.003). In multivariate analysis, ECOG PS 2, grade III histology, and brain or bone metastasis negatively affected OS, whereas BMI ≥ 25 kg/m2 positively affected OS. A high BMI prior to therapy in patients with NSCLC treated with platinum-based ChT in the first-line setting was associated with more favorable PFS and OS.

Efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer.

Aim: To evaluate the efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer. Methods: We retrospectively included 138 patients who were given trastuzumab-based chemotherapy as first-line treatment and analyzed the relationship between clinical response rates and maintenance treatment status and survival outcomes. Results: In the whole group, the median progression-free survival and overall survival were 10.2 and 16 months, respectively. Clinical response was obtained in 79% of patients. The median overall survival was 16.9 months in follow-up group and 19.0 months in the maintenance group in patients with clinical response. Continuation of maintenance trastuzumab created a significant survival advantage (p = 0.021). Eastern Cooperative Oncology Group performance status 2 (hazard ratio [HR]: 2.02), grade 3 (HR: 1.78) and more than four metastatic lesions (HR: 1.67) were determined as risk factors for death. Conclusion: We recommend the continuation of maintenance trastuzumab in patients with clinical response, but those with identified risk factors may not benefit from treatment because life expectancy may be low.

Gastric cancer has a poor prognosis despite available treatments. Inclusive studies are still needed with real-life data. Our research retrospectively evaluated the efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer who received trastuzumab-based chemotherapy as first-line therapy. In total, 138 patients were included in this study. Clinical response to trastuzumab-based chemotherapy was obtained in 79% of the patients. We also divided the patients who had a clinical response into two groups according to whether they received maintenance therapy. In the present study, trastuzumab administration had compatible survival outcomes with recent studies. Continuation of trastuzumab maintenance treatment provided a survival advantage in patients with clinical response. We suppose that maintenance trastuzumab may be recommended in patients with clinical responses to the first-line treatment. Furthermore, Eastern Cooperative Oncology Group Performance Status 2, grade 3 and having more than four metastatic lesions were determined as risk factors for death. Therefore, although we recommend maintenance of trastuzumab in patients with clinical response, those with identified risk factors may not benefit from treatment.

The conversion of RAS status in metastatic colorectal cancer patients after first-line biological agent treatment.

AIM: The aim was to investigate the RAS discordance between initial and recurrent metastasectomy specimens in metastatic colorectal cancer (mCRC) patients treated with chemotherapy (CT) plus biological agents in a first-line setting. METHODS: Patients who had been treated with CT plus bevacizumab or cetuximab or panitumumab followed by R0 resection for potentially resectable colorectal cancer liver metastases were scanned. Among these, patients who developed resectable new metastases after a disease-free interval longer than 6 months were included in the study. We compared the RAS mutation status between the first biopsy and the second metastasectomy specimen. RESULTS: A total of 82 mCRC patients treated with CT plus biological agents in a first-line setting were included in the study. The first biopsy assessment showed wild-type RAS tumours in 39 (47.6%) patients and mutant RAS tumours in 43 (52.4%) patients. The mean time for new operable liver metastasis after R0 resection was 15.5 months. In the second metastasectomy specimens, the numbers of wild-type and mutant RAS tumours were 30 (36.6%) and 52 (63.4%), respectively. The comparison with the first biopsy specimens showed RAS status conversions in 17 (20.7%) patients. Univariate comparison between patients with and without RAS status conversion revealed that grade, pathological T stage, wild-type RAS tumour and longer biological agent use time in the first-line treatment were significant factors for RAS conversion. CONCLUSION: Our results suggest that re-biopsy is needed for an optimal second-line treatment decision in mCRC patients regardless of backbone biological agent, especially in patients with wild-type RAS mCRC.

The impact of tumor regression grade on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy.

PURPOSE: The aim of this study is to investigate the prognostic effect of tumor regression grade (TRG) on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy. METHODS: Medical records of 182 patients with locally advanced rectal cancer, who were treated with preoperative chemoradiotherapy followed by surgery between 2002 and 2016, were retrospectively reviewed. TRG was classified into five categories based on the pathological response as follows - TRG1: no viable cancer cell, TRG2: single cancer cell or small groups of cancer cells, TRG3: residual tumor outgrown by fibrosis, TRG4: residual tumor outgrowing fibrosis, TRG5: diffuse residual tumor without regression. TRG1, (TRG2+TRG3), and (TRG4+TRG5) were grouped as complete response, intermediate response, and no response, respectively. RESULTS: Of the 182 patients with locally advanced rectal cancer, 112 (61.5%) were male. The mean age was 54.4 (range, 25-87) years. The total number of patients in complete response, intermediate response, and no response group was 24 (13.2%), 105 (57.7%), and 53 (29.1%), respectively. The corresponding five-year relapse-free survival and overall survival rates were 79.8%-92.3%, 74.7%-79.4%, and 55.7%-55.8%, respectively (p < 0.05 for relapse-free survival, p < 0.05 for overall survival). According to ypTNM stage, there was no significant difference in relapse-free survival among TRG groups in ypStage I and II patients (p > 0.05). In ypStage III patients, relapse-free survival was 62 months in no response group vs. not reached in intermediate response group (p < 0.05). According to the ypTNM, there was no significant difference in overall survival among TRG groups in ypStage I, II, and III patients (p > 0.05). In the multivariate analysis, pathological complete response was found to be an independent variable for relapse-free survival and overall survival (hazard ratio (95% confidence interval), 0.34 (0.17-6.77), 0.39 (0.18-0.83), respectively). CONCLUSION: This study showed that patients with pathological complete response to preoperative chemoradiotherapy had longer relapse-free survival and overall survival rates than those with residual disease.

The predictive role of metabolic tumor volume on no response to neoadjuvant chemotherapy in patients with breast cancer.

INTRODUCTION: To evaluate the predictive significance of pretreatment metabolic tumor volume on pathologic response in patients who received neoadjuvant chemotherapy for breast cancer. METHODS: Seventy patients who received neoadjuvant chemotherapy between 2013 and 2017 years were enrolled in the study. Pathologic responses and 18-fluorodeoxyglucose positron emission tomography/computed tomography metabolic dates of patients were obtained from archive files. RESULTS: Forty-six (65.7%) patients were in stage II and 24 (34.3%) patients were in stage III; 25 (35.7%) patients were human epidermal growth factor receptor 2 positive, 46 (65.7%) patients were estrogen receptor-positive, 26 (37.1%) patients were progesterone receptor-positive. According to the Miller-Payne grading system, 24 (34.3%) patients constituted 100% pathological response; patients with 91-99% pathological response were 12 (17.1%), the number of patients with non-pathologic response was 6 (8.6%). Median metabolic tumor volume was 7.3 cm3 (7.1 ± 3.5), 8.8 (11.4 ± 9.4), 7.7 (8.3 ± 4.6) and 22 cm3 (19.8 ± 11.0) in patients with stages IIA, IIB, IIIA, and IIIB, respectively (p = 0.032). In Miller-Payne grading, the median metabolic tumor volume value was higher in patients with no pathologic response group than 100% response group (p = 0.003). The cut-off metabolic tumor volume value determining no pathologic response was calculated as higher than 13.62 cm3 (sensitivity 83.3% and specificity 82.8%). CONCLUSIONS: Our study results suggest that higher pretreatment metabolic tumor volume values are predictive on no pathologic response in patients treated with neoadjuvant chemotherapy for breast cancer.

Efficacy and tolerability of adjuvant therapy in ≥70-year-old patients with T3N0M0 colorectal cancer: An observational study.

BACKGROUND: This study aimed to retrospectively investigate the efficacy and tolerability of adjuvant chemotherapy in ≥70-year-old patients with stage IIA (T3N0M0) colorectal cancer. METHODS: Lymphovascular invasion, perineural invasion, margin positivity, dissected lymph node count of <12, and presence of perforation/obstruction were accepted as risk factors. Those patients with at least one risk factor were regarded as having high risk. RESULTS: The study included 168 patients, among which 95 (56.5%) were male and 73 (43.5%) were female. The median age of patients was 73 years (range: 70-94). One hundred one (60.1%) patients were identified to have high risk. Eighty-one (87%) patients received 5-flourouracil+leucovorin and 12 (13%) patients received capecitabine regimens as adjuvant chemotherapy. The patients receiving capecitabine regimen had significantly higher rates of dose reduction at initiation and during the treatment. Among low-risk group, there was no statistically significant difference between patients with and without adjuvant chemotherapy in terms of disease-free survival or overall survival (p = 0.528 and p = 0.217, respectively). In high-risk group, patients receiving adjuvant chemotherapy significantly differed from those not receiving adjuvant chemotherapy in terms of median disease-free survival and overall survival (p = 0.009 and p < 0.001, respectively). While the grade, lymph node status, and adjuvant chemotherapy were identified as the most significant independent factors for disease-free survival, the most significant factors for overall survival were the age, Eastern Cooperative Oncology Group performance status, adjuvant chemotherapy, and recurrence. CONCLUSION: The findings of our study showed improved disease-free survival and overall survival in high-risk ≥70-year-old patients who received adjuvant chemotherapy due to T3N0M0 colorectal cancer. We believe that 5-flourouracil+leucovorin or capecitabine regimens should be recommended for these older high-risk patients who could receive adjuvant chemotherapy regardless of age.

Factors Affecting Disease-Free Survival in Operated Nonmetastatic Gastrointestinal Stromal Tumors.

BACKGROUND: Possibly originating from interstitial Cajal cells, gastrointestinal stromal tumors (GISTs) have variable biological behaviors. In this study, we aimed to examine the factors affecting the disease-free survival (DFS) in patients with GIST who underwent operation. MATERIAL AND METHODS: The study included the patients who were followed up and treated for GIST in our oncology clinic between 2002 and 2017. The Armed Forces Institute of Pathology criteria (Miettinen risk score) were used for risk stratification of patients. RESULTS: Seventy-four patients were included to the study, where female patients constituted 52.7%, and the median age was 56 (range: 24-83) y. Most common primary tumor location was the stomach (51.4%), followed by the small intestine (33.8%), colorectum (10.8%), and retroperitoneum (4.1%). Miettinen risk score showed 12 patients (16.7%) at very low risk, 15 patients (20.8%) at low risk, 18 patients (25%) at intermediate risk, and 27 patients (37.5%) at high risk. DFS was significantly lower in patients with small intestine involvement than in cases with stomach involvement (P = 0.004). DFS was significantly lower in patients at high risk than in patients with no high risk (P = 0.034). Small intestine localization (hazard ratio [HR], 8.98; 95% confidence interval [CI], 1.14-8.18), high-risk score (HR, 5.16; 95% CI, 1.42-12.75), c-kit positivity (HR, 0.24; 95% CI, 0.13-0.69), and adjuvant therapy (HR, 0.37; 95% CI, 0.20-0.92) were found to be the most significant factors affecting DFS. CONCLUSIONS: Our study showed negative effects of small intestine localization and high-risk category and positive effects of c-kit positivity and adjuvant therapy on DFS in patients with GIST who underwent operation. When a decision will be made in favor of adjuvant therapy, tumor localization and c-kit mutation should also be considered in addition to risk score.

FOLFIRI plus panitumumab in the treatment of wild-type KRAS and wild-type NRAS metastatic colorectal cancer.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of first-line panitumumab plus folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) in patients with wild-type KRAS and wild-type NRAS metastatic colorectal cancer (mCRC). METHODS: Patients with wild-type KRAS and wild-type NRAS mCRC presenting to the medical oncology department of the Okmeydani Training and Research Hospital in Istanbul, Turkey, between April 2014 and January 2018 were enrolled in this study. RESULTS: A total of 64 patients (35 males and 29 females) with a median age of 59 (35-81) years old were enrolled. The median follow-up was 18.9 months, and the median progression-free survival was 13 months. The median overall survival (OS) was 26 months in the patients with wild-type KRAS and wild-type NRAS mCRC. It was 90.4% for the 6-month OS, 79.5% for the 1-year OS, 53.7% for the 2-year OS and 31.1% for the 3-year OS. The median OS of the patients who underwent metastasectomies was 40 [95% confidence interval (CI) = 19.9-60.1] months, and the median OS of the patients without metastasectomies was 22 (95% CI = 17.7-26.4) months. There was a statistically significant difference between these (P = 0.007). CONCLUSION: The first-line FOLFIRI plus panitumumab was associated with favourable efficacy in the patients with wild-type KRAS and wild-type NRAS mCRC, and it was well tolerated. The removal of the metastases that became resectable after chemotherapy further prolonged the patients' survival. TRIAL REGISTRATION: Retrospectively registered: 33886.

Prognostic value of ERCC1, ERCC2, XRCC1, and TP53 single nucleotide polymorphisms in patients with early-stage non-small cell lung cancer.

Identification of biomarkers used for the prognostic evaluation of non-small cell lung cancer (NSCLC) patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in completely resected NSCLC patients. In total, 130 patients, surgically treated for NSCLC between 2000 and 2012, were included. An analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln, and TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan-Meier method and Cox regression analysis were used. Median age rate was 59.3, ranging between 36 and 78 years. Median relapse-free survival duration (RFS) was found as 46.2 months. In those with ERCC2 CC allele, median RFS was detected as 28.3 months (95 % confidence interval (CI), 20.8-35.8), 46.9 months in those with CT heterozygous (95 % CI, 18.6-75.2), and 80.1 months for those with TT mutant allel (95 % CI, 33.0-127.2). Median RFS was seen to be longer in mutant group and also statistically significant (P = 0.018). Additionally, upon evaluating CC normal group with CT + TT alleles including mutant alleles, median RFS was found as 56.5 months (95 % CI, 24.6-88.4) in CT + TT group, and this was statistically significant (P = 0.005) Also, median RFS was 15.1 months in those including ERCC2 CC allele and 56.5 months in CT + TT allele in the group with no adjuvant treatment (P = 0.001). In conclusion, our study showed that ERCC2/XPD polymorphism is an independent prognostic factor in operated NSCLC patients, and these findings should be supported with prospective studies.

Prognostic factors for gemcitabine-refractory patients with advanced pancreatic cancer: a retrospective analysis of a multicentre study (Anatolian Society of Medical Oncology).

AIM OF THE STUDY: Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of the study was to search for prognostic factors for survival in patients with gemcitabine (Gem)-refractory or with gemcitabine and cisplatin (GemCis)-refractory advanced pancreatic cancer. MATERIAL AND METHODS: We retrospectively evaluated patients with Gem- or GemCis-refractory advanced pancreatic cancer. Sixteen potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. Univariate and multivariate statistical methods were used to determine prognostic factors. RESULTS: Multivariate analysis included the four prognostic significance factors in univariate analysis. Multivariate analysis showed that liver metastasis and second-line chemotherapy were considered independent prognostic factors for survival. CONCLUSIONS: Liver metastasis and second-line chemotherapy were identified as important prognostic factors in advanced pancreatic cancer patients refractory to treatment with Gem or GemCis. This prognostic factors may also facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.

Clinicopathologic Features and Efficacy of Induction Chemotherapy in Nasopharyngeal Carcinoma: Real-World Experience.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) accounts for 0.01% of all carcinomas, and 70% of patients have locally advanced disease with a poor prognosis. The mainstay therapy is chemoradiotherapy (CRT), and concurrent administration of platinum-based agents and irradiation provides high local control rates. However, induction (neoadjuvant) chemotherapy (ICT) prior to CRT is recommended for large tumors with a high tumor burden at the category 1 level. For ICT, platinum-based doublet or triplet combination regimens are recommended. Selected patients with a high tumor burden at the time of diagnosis who did not receive ICT before CRT were given adjuvant (consolidation) therapy after CRT. This multicenter study aimed to share our experience in treatment of NPC and evaluate the factors associated with survival. METHODS: The study included patients diagnosed with NPC who were followed and treated between 2008 and 2022. Hundred and forty-two patients from 6 centers were evaluated. The factors associated with disease-free survival (DFS) and overall survival (OS) were evaluated. RESULTS: The median age of our patients was 51 years (IQR: 16-81 years), and the male:female ratio was 2.5:1. A majority of patients (71%) had stage 3-4 disease. They had locally advanced disease, and 48 patients (34%) received ICT. Twenty patients (14%) received adjuvant therapy. The median follow-up was 41 months (range, 2.7-175.1 months). The median DFS in NPC was 92.6 months (range, 71.9-113.3 months), with a 40th month DFS of 70.9%. The median OS was 113 months (range, 91-135 months), with a 40th month OS of 84.7%. Median DFS was 95.3 months (range, 64.2-126.4 months) in patients who received ICT before CRT, which was longer than in the CRT-only group (p = 0.6). DFS at the 40th month was 75.1% in patients treated with ICT compared to 65.1% in the CRT-only group. Median OS was 117 months (range, 92-142 months) in patients receiving ICT, which was longer than in the CRT-only group (p = 0.4). OS at the 40th month was 86.7% in patients receiving ICT but 83.6% in the CRT-only group. CONCLUSIONS: Both the objective response rate and survival were longer in patients who radiologically responded to CRT following ICT. Nonresponse to ICT is a negative predictive indicator. The role of ICT in locally advanced NPC is increasing.

Childhood, adolescents, and young adults (≤25 y) colorectal cancer: study of Anatolian Society of Medical Oncology.

PURPOSE: To evaluate the clinicopathologic characteristics and treatment outcomes of young patients with colorectal cancer (CRC). METHODS: Between May 2003 and June 2010, 76 patients were found eligible for this retrospective study. Age, sex, presenting symptoms, patients with acute presentation, family history, presence of polyps, histologic features, localization and stage of the tumor, treatment outcomes, time and site of recurrence, sites of metastasis, and survival outcomes were recorded from the patient files. RESULTS: Seventy-six patients (55.3% male) with a median age of 23 years were evaluated. Patients were evaluated in 2 groups as follows: child-adolescent (0 to 19 y, n=20) and young adult (20 to 25 y, n=56). Sex and symptoms (abdominal pain and rectal bleeding) were significantly differed between the groups and acute presentation was close to statistical significance. Overall survival significantly increased in patients undergoing curative surgery (P<0.001). Other parameters affecting the survival was stage of disease (P=0.004). Response to palliative chemotherapy in metastatic patients (P=0.042) and postoperative adjuvant chemotherapy had a statistically significant survival advantage (P=0.028). CONCLUSIONS: Diagnosis of CRC should not be excluded solely on the basis of age. CRC features in young-adult patients are more similar to adults compared with that of child-adolescent patients according to the symptoms and presentation. In patients with CRC in this age group, curative surgery, adjuvant chemotherapy, and palliative chemotherapy provide survival advantage.

The Prognostic Role of Mismatch Repair Status and CDX-2 Expression with Inflammatory Markers and Pathological Risk Factors in Stage II and III Colon Cancer: Multicenter Real-Life Data.

OBJECTIVE: Colorectal cancer is common worldwide, and adjuvant treatment's benefit is still controversial. We designed this study to determine the role of MSI and CDX-2 status determined by immunohistochemistry (IHC) combined with the inflammatory markers and pathological parameters in predicting disease recurrence in stage II and III colon cancer. METHODS: A total of 226 stage II/III colon cancer patients with a median age of 59 years who underwent initial surgery were included in this retrospective study. The pathologic assessment of MSI and CDX-2 was performed twice by immunohistochemistry (IHC) and two different pathologists. No staining/weak staining below 10% of the tumor was accepted as CDX-2 negative, and any MSI clones with weak staining below 10% were accepted as MSI-H. The laboratory parameters were noted at the initial diagnosis. RESULTS: One hundred twenty-one and 105 patients were diagnosed with stage III and II colon cancer. 58.0% of patients were male, 46 (20.4%) of tumor tissue were MSS, and 17 (7.5%) were CDX-2 negative. One hundred twenty-nine tumors were localized in the right colon. Disease recurrence was significantly correlated with tumor localization, CDX-2 status, stage at diagnosis, and preoperatively median CRP and CEA levels. DFS rates for MSS patients with CDX-2 negative and positive were 36.7% and 98.1%, respectively [p < 0.001]. There was no significant correlation between MSI status and CDX-2 status. MSI status, the presence of adjuvant treatment, and systemic inflammatory markers were not significant prognostic factors for DFS. CDX-2 status [HR:0.08, CI 95% 0.03-0.17, p < 0.001 HR: 1.7, CI 95% 1.1-3.0, p = 0.03], disease stage [HR:2.6, CI 95% 1.43-4.74], and preoperatively CEA levels [HR:4.1 CI 95% 2.18-785, p < 0.001 were independent significant prognostic factors for DFS. CONCLUSION: CDX-2 loss was an independent prognostic factor for DFS and disease recurrence in early-stage colon cancer. MSS patients with CDX-2 loss had significantly worse survival outcomes, and this might be the reason for deciding on adjuvant chemotherapy.

The XRCC1 and TP53 gene polymorphisms are associated with advanced-stage disease and early distant metastasis at diagnosis in non-small cell lung cancer.

Background: Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC. Objective: This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC. Material and Methods: In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis. Results: The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031). Conclusions: We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

The effect of concomitant proton pump inhibitor use on survival outcomes of Nivolumab-treated renal cell carcinoma patients: a multicenter study.

AIM: We aimed to evaluate the effect of concomitant proton pump inhibitors (PPI) use with nivolumab on survival outcomes in metastatic renal cell carcinoma (mRCC) in second-line setting. METHODS: The study was designed as a multicenter and retrospective involving patients with metastatic renal cell carcinoma receiving second-line nivolumab therapy. One hundred and nine patients with mRCC were divided into two groups based on whether they use PPI concomitantly with nivolumab: concomitant PPI users and non-users. Overall survival (OS) and progression-free survival (PFS) were compared between the groups with and without concurrent PPIs. RESULTS: Of 109 patients in our study, 59 were not using PPI concomitantly with nivolumab and 50 were using PPI concomitantly. The median PFS was 6.37 (5.2-7.5) months in the concomitant PPI group and 9.7 (4.5-15) months in the non-users (p = 0.03). The median OS was 14.6 (7.1-22.1) months in patients on PPI concurrently with nivolumab and 29.9 (17.1-42.7) months in the non-users (p = 0.01). Accordingly, PPI use for PFS (Non-use vs. Use = HR: 0.44, 95%Cl 0.28-0.96, p = 0.014) and PPI use for OS (Non-use vs. Use = HR: 0.68, 95%Cl 0.22-0.88, p = 0.01) were found to be as independent risk factors. CONCLUSIONS: Concomitant use of PPIs is associated with worse survival outcomes in patients with mRCC treated with nivolumab. Clinicians should carefully consider the concomitant use of PPIs in such patients.