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.

Clinicopathological Features and Prognosis of Invasive Micropapillary Carcinoma Compared to Invasive Ductal Carcinoma-NOS: Worse or Better?

OBJECTIVE: To evaluate whether there are differences in invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma-NOS (IDC-NOS) according to the clinicopathological features and prognosis including molecular subtypes. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Pathology, University of Health Sciences, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey, from 2003 to 2016. METHODOLOGY: Operated breast cancer cases (58 IMPC + 326 IDC-NOS), with long-term follow-up findings (cases followed up until 2020), were reviewed. The cases, whose other component was only IDC-NOS, were included in the mixed IMPC group. The clinical features, including clinical presentation, treatments, and follow-up information were obtained from the patient clinical database. The IMPC cases included in the study were re-examined, and micropapillary tumour components were confirmed based on the criteria set by the World Health Organisation (WHO). The clinicopathological findings, recurrence, and survival data of both groups were compared. In addition, IDC-NOS was divided into the molecular subgroups and compared with IMPC cases in terms of 5-year overall survival (OS). RESULTS: There was no significant difference between the two groups for the distribution of molecular subtypes. There was a statistically significant difference among the nuclear grade, tumour size, nodal status, lymphovascular, and perineural invasion. In the first 5-year period, the OS rate for IDC-NOS and IMPC was 90.8% and 86.2% (p<0.05). The 5-year OS rate of luminal A, luminal B, HER2, triple negative (TN), and IMPC patients was 97.6%, 91.3%, 90%, 70%, and 86.2%, respectively (p<0.05). The OS rate in patients with TN and IMPC was similar which was found significantly lower than the other groups (luminal A, luminal B, and HER2). The median OS was 51.3 months and 53.9 months for the patients with TN and IMPC, respectively (p<0.001). This difference disappeared in the 10th and 15th years of follow-up. CONCLUSION: The majority of the deaths in IMPC occurred within the first 5 years. The 5-year OS rates were similar in the TN and IMPC patients. The survival pattern of IMPC is parallel with TN, Therefore, clinical, therapeutic, and prognostic evaluation in IMPC can be done like TN. KEY WORDS: Invasive ductal carcinoma, Invasive micropapillary carcinoma, Survival.

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.

Targeted axillary biopsy and sentinel lymph node biopsy for axillary restaging after neoadjuvant chemotherapy.

PURPOSE: Accurate restaging of the axilla after neoadjuvant chemotherapy (NAC) is an important issue to ensure deescalating axillary surgery in patients with initial metastatic nodes. We aimed to present our results of targeted axillary biopsy (TAB) combined with sentinel lymph node biopsy (SLNB) for axillary restaging after NAC. METHODS: In 64 breast cancer patients who underwent NAC, biopsy-proven positive nodes were marked with clips before NAC, and ultrasound-guided wire localization of clip-marked nodes was performed after NAC. Patients underwent TAB and SLNB for post-NAC axilla restaging. RESULTS: Identification rates of post-NAC TAB and SLNB were 98.4% and 87.5%, respectively (P = 0.033). Histopathology revealed a nodal pathologic complete response (pCR) rate of 47% in which axillary lymph node dissection (ALND) was avoided. TAB alone and SLNB alone detected residual disease in 29 (85.3%) and 20 (58.8%) patients (P = 0.029), respectively. Whereas rates of up to 97% had been achieved with a combination of TAB and SLNB. The pCR rates after NAC were 64.3% for human epidermal growth factor receptor 2 positive and triple-negative tumors and 13.6% in luminal tumors (P = 0.0002). CONCLUSION: Pathologic analysis following TAB combined with SLNB revealed the pCR rates to NAC in a considerable number of patients that provided de-escalation of axillary surgery. A combination of SLNB and TAB was found to be an accurate procedure in establishing residual nodal disease. This combined procedure in patients with initially positive nodes was a reliable method for post-NAC axillary restaging.

Pathological Complete Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer: The Relationship Between Inflammatory Biomarkers and Molecular Subtypes.

Purpose Among patients with breast cancer, pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is an important prognostic predictor of survival. This study aimed to investigate the relationship between platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) along with overall pCR. Method A total of 150 patients with breast cancer who were first administered NAC and then operated on were retrospectively evaluated. Neutrophil-lymphocyte ratio and PLR obtained from the complete blood count analysis performed immediately before NAC treatment were analyzed. The cut-off value was calculated as 150 for PLR and 2.24 for NLR. We studied the predictive value of NLR and PLR levels for the pathologic response of breast cancer to NAC. Results Pathological complete response was observed in 34.7% (n = 52) of the patients, pCR in the breast in 42.7% (n = 64), and that in the axilla in 44% (n = 66). There was a statistically significant difference between the pCR rates according to the PLR levels (p = 0.013). In addition, a statistically significant difference was found in the pCR rates in the breast and axilla according to PLR levels (p = 0.018, p = 0.009). Patients with low PLR in the human epidermal growth factor receptor 2 (HER-2) group had significantly higher axillary pCR rates than in those with high PLR (p = 0.019). Conclusions A low PLR level showed high chemotherapy sensitivity independent of molecular subtypes in the treatment of breast cancer with NAC. The PLR level can serve as a predictive marker of the therapeutic effect of NAC on the breast and axilla. Low PLR levels in HER-2 enriched groups can predict pCR in the axilla.

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

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

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

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

Simultaneous resection for colorectal cancer with synchronous liver metastases is a safe procedure: Outcomes at a single center in Turkey.

The optimal surgical strategy for treating colorectal cancer with synchronous liver metastases is subject to debate. The current study sought to evaluate the outcomes of simultaneous colorectal cancer and liver metastases resection in a single center. Prospectively collected data on all patients with synchronous colorectal liver metastases who underwent simultaneous resection with curative intent were analyzed retrospectively. Patient outcomes were compared depending on the primary tumor location and type of liver resection (major or minor). Between January 2005 and August 2016, 108 patients underwent simultaneous resection of primary colorectal cancer and liver metastases. The tumor was localized to the right side of the colon in 24 patients (22%), to the left side in 40 (37%), and to the rectum in 44 (41%). Perioperative mortality occurred in 3 patients (3%). Postoperative complications were noted in 32 patients (30%), and most of these complications (75%) were grade 1 to 3 according to the Clavien-Dindo classification. Neither perioperative mortality nor the rate of postoperative complications after simultaneous resection differed among patients with cancer of the right side of the colon, those with cancer of the left side of the colon, and those with rectal cancer (4%, 2.5%, and 2%, respectively, p = 0.89) and (17%, 33%, and 34%, respectively; p = 0.29)]. The 5-year overall survival of the entire sample was 54% and the 3-year overall survival was 67 %. In conclusion, simultaneous resection for primary colorectal cancer and liver metastases is a safe procedure and can be performed without excess morbidity in carefully selected patients regardless of the location of the primary tumor and type of hepatectomy.

Modified docetaxel, cisplatin and fluorouracil therapy as the first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck cancer: a retrospective study.

AIM: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) therapy has been shown to be a well tolerated and highly effective regimen for metastatic gastric carcinoma. Herein we investigated the effectiveness of the mDCF combination as the first-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC). METHODS: A total of 80 patients with recurrent/metastatic HNSCC who were treated with mDCF between 2009 and 2015 were enrolled into this study. All patients were treated in the first-line with 2-6 cycles of mDCF chemotherapy which consisted of docetaxel 60 mg/m2 intravenously (IV) on day 1, cisplatin 60 mg/m2 IV on day 1, and 5-fluorouracil 600 mg/m2 IV for 5 days of continuous infusion, with cycles repeated every 21 days. RESULTS: The most common grade 3-4 toxicities were neutropenia (22.5%), anemia (10%), thrombocytopenia (7.5%), nephrotoxicity (1.3%), hepatotoxicity (1.3%), and diarrhea (2.5%). Twelve patients (15%) experienced a febrile neutropenic episode. Dose modification was required in 22 (27.5%) of the patients due to drug toxicity. Complete response was achieved in 2.5% of all patients, while partial and stable responses were reported to be 43.8% and 25%, respectively, with a disease control rate of 71.3%. The median progression-free and overall survival was 7 (95% CI: 5.3-8.6) and 11.5 (95% CI: 9.4-13.7) months, respectively. CONCLUSIONS: The efficiency of the mDCF combination for induction chemotherapy has been well established previously. To our knowledge, this is one of the largest studies evaluating the survival and safety significance of mDCF chemotherapy as a first-line treatment in patients with recurrent/metastatic HNSCC.

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

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

Evaluation of prognostic factors and treatment in advanced small bowel adenocarcinoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology (ASMO).

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Since these are rarely encountered tumors, there are limited numbers of studies investigating systemic treatment in advanced SBA. The purpose of this study was to evaluate the prognostic factors and systemic treatments in patients with advance SBA. METHODS: Seventy-one patients from 18 Centers with advanced SBA were included in the study. Fifty-six patients received one of the four different chemotherapy regimens as first-line therapy and 15 patients were treated with best supportive care (BSC). RESULTS: Of the 71 patients, 42 (59%) were male and 29 (41%) female with a median age of 56 years. Median follow- up duration was 14.3 months. The median progression free survival (PFS) and overall survival (OS) were 7 and 13 months, respectively (N=71). In patients treated with FOLFOX (N=18), FOLFIRI (N=11), cisplatin-5-fluorouracil/ 5-FU (N=17) and gemcitabine alone (N=10), median PFS was 7, 8, 8 and 5 months, respectively, while median OS was 15, 16, 15 and 11 months, respectively. No significant differences between chemotherapy groups were noticed in terms of PFS and OS. Univariate analysis revealed that chemotherapy administration, de novo metastatic disease, ECOG PS 0 and 1, and overall response to therapy were significantly related to improved outcome. Only overall response to treatment was found to be significantly prognostic in multivariate analysis (p=0.001). CONCLUSIONS: In this study, overall response to chemotherapy emerged as the single significant prognostic factor for advanced SBAs. Platin and irinotecan based regimens achieved similar survival outcomes in advanced SBA patients.

The Association Between JAK2V617F Mutation and Bone Marrow Fibrosis at Diagnosis in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms.

OBJECTIVE: Bone marrow fibrosis is the second most common complication that causes morbidity and mortality inpatients with Philadelphia-negative myeloproliferative neoplasms (MPNs). The aim of this study was to investigate theassociation between JAK2V617F mutation and bone marrow fibrosis at diagnosis in patients with MPNs. MATERIAL AND METHODS: In total, 149 patients with MPNs were retrospectively evaluated to determine if there was anassociation between the histological grade of bone marrow fibrosis and JAK2V617F mutation. RESULTS: In all, 67.7% of the patients carried the mutated JAK2 gene. The presence of JAK2V617F mutation was notassociated with the occurrence of bone marrow fibrosis (P=0.55) or its grade at diagnosis (P=0.65). CONCLUSION: Molecular mechanisms or genetic defects other than JAK2V617F may underlie the occurrence of bonemarrow fibrosis in patients with MPNs.

Evaluation of thyroid nodules in Turkish population.

OBJECTIVE: To determine the characteristics of thyroid nodules by using fine needle aspiration (FNA) biopsy and ultrasonography. PATIENTS AND METHODS: FNAs of 1,004 patients with thyroid nodules between 2000 and 2007 were evaluated retrospectively. The surgical records of 101 of the patients were available and reviewed. The Odds ratios for nodule characteristics were calculated individually. RESULTS: The sensitivity of FNA was 66.7% and the specificity was 95.2%. Positive predictive value was 72.7% and negative predictive value was 93.7%. Our diagnostic accuracy was 90.5%. Solitary nodules, irregular margins and microcalcifications were associated with increased risk of malignancy with Odds ratios 3.61 (95% CI: 1.25-10.42; p= 0,017); 5.44 (95% CI: 1.76-16.78; p= 0,003) and 39.29 (95% CI 8.32-185.47; p< 0.001) respectively. Macrocalcification, age, gender and thyroid status were not associated with increased risk of malignancy. CONCLUSION: Our data suggest that FNA is a reliable, reproducible and valid method to evaluate thyroid nodules and ultrasonographic features, especially microcalcification is a very important predictor of malignancy.