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.

Psychological impacts of COVID-19 pandemic in cancer patients on active treatment.

Introduction: Although cancer patients have a high risk of exposing COVID-19 and developing severe complications, they have to receive active treatment. We aimed to determine the psychological conditions of cancer patients and shed light on the establishment of early psychological intervention and intervention policies by making specific recommendations. Method: We consecutively evaluated 385 cancer patients under treatment. Post-traumatic stress disorder (PTSD) symptoms, depression, anxiety, stress, and associated sociodemographic/clinical characteristics were investigated. In addition, we applied depression-anxiety-stress-scale-21 (DASS-21) for the mental states of patients and Impact of Event-Scale-Revised (IES-R) for the psychological effects of Covid-19. Results: The mean age was 58 (18-88). 47.2% were psychologically distressful per DASS-21, and 39.3% were traumatic per IES-R scores. 71.9% stated the risk of getting COVID-19 was high since they had cancer, and 82% stated serious complications would develop if they had COVID-19 infection. Patients diagnosed for more than one year were more stressed, anxious, and depressive (p-value = 0.001,0.003,0.049, respectively). Singles were more stressed, depressed, and traumatized than couples (p-value = 0.001, 0.011, 0.001). In multivariate analysis, a significant correlation with being under psychiatric treatment before the pandemic was found for depression (OR: 3.743, 95 %CI: 1.790-7.827) anxiety (OR: 3.776-95 %CI: 1.945-7.332) and stress levels (OR: 4.129, 95 %CI: 1.728-9.866). Having relatives who died or received treatment for COVID-19(OR: 0.515,0.296-0.895) and being unmarried (OR: 2.445-95% CI: 1.260-4.747) predicts PTSD development. Conclusions: When the psychological effects of the COVID-19 pandemic are manifesting strongly, cancer patients' anxiety and exposure levels are high. It is of great importance that clinicians understand needs, recognize psychological distress, and direct them to relevant departments for supportive care.

Efficacy and safety of trastuzumab emtansine in older patients with HER2-positive advanced breast cancer: a real-world study.

INTRODUCTION: Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate and its survival advantage has been shown in advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, clinical trials underrepresent patients ⩾65 years of age, leading to a lack of information in this population. We analyzed the real-world outcomes of older women who were treated with T-DM1 therapy. METHODS: We performed a multicenter, observational, retrospective analysis of patients aged ⩾65 years treated with T-DM1. A total of 93 patients from 10 cancer centers were involved in the study. Our goal was to determine the survival, response rates, and toxicity profile in T-DM1-treated patients, as well as the factors that influence survival. RESULTS: Median follow-up was 12.2 months. Objective response rate was 29%. Median progression-free survival (PFS) and overall survival (OS) were 8.47 and 15.0 months, respectively. In multivariate analysis, Eastern Cooperative Oncology Group Performance Score 2 was found to be an independent prognostic factor for worse PFS (hazard ratio [HR] 1.81, p = 0.032) and OS (HR 2.33, p = 0.006). Any adverse event (AE) was seen in 92.5% of patients; grade 3 or 4 AEs were seen in 30.1%. Dose reduction or treatment discontinuation rates were 11.8% and 6.5%, respectively. CONCLUSION: The efficacy of T-DM1 was acceptable and it was generally well-tolerated among older patients with advanced HER2-positive breast cancer.

Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?

PURPOSE: Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment. METHODS: Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin × fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. RESULTS: Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2), p = 0.01]. CONCLUSION: Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.

Preclinical discovery and clinical development of encorafenib for the treatment of melanoma.

INTRODUCTION: Nearly 50% of patients with metastatic melanoma harbor a BRAFV600-mutation, which can be targeted with the use of BRAF and MEK inhibitors, either in the front-line or treatment-refractory setting. Encorafenib is the newest BRAF-inhibitor to have received FDA-approval in combination with the MEK inhibitor binimetinib. AREAS COVERED: The authors provide an overview of the preclinical development and the clinical trials that led to the use of encorafenib in BRAFV600-mutant melanoma. They also give discussion on its current use in clinical practice, providing their expert perspectives on the subject. EXPERT OPINION: Preclinical research has provided strong rationale for upgrading encorafenib investigation into clinical development/testing. However, there is not yet enough data to determine where encorafenib may fit in comparison to other drugs in the same class, and ongoing trials will further define its role in the treatment of melanoma. Of note, there are ongoing studies that further explore the role of encorafenib + binimetinib such as in combination regimens with immunotherapy drugs, and in brain metastases.

Does primary tumor localization has prognostic importance in seminoma patients?: Turkish Oncology Group Study.

PURPOSE: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients. METHODS: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study. RESULTS: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007). CONCLUSION: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.

VEGF-VEGFR pathway seems to be the best target in hepatic epithelioid hemangioendothelioma: A case series with review of the literature.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor originating from endothelial cells. Clinical aspect of the disease covers a wide spectrum from a low-grade tumor to a fatal cancer. Most common sites of EHE are reported as lung, liver and bone. Hepatic EHE (HEHE) is a clinical form with an incidence of less than 1 person in a million. Due to rarity of the disease, there is no standard therapy established. Surgery and liver transplantation still seem to be the best approach if possible. However, most of the patients present with unresectable or metastatic disease. Many conventional chemotherapeutic agents and antiangiogenic drugs have been reported previously in the literature with inconsistent outcomes. Here we report 4 cases of HEHE, who benefit distinctly from anti-VEGF treatments in different settings. While combination of paclitaxel and bevacizumab resulted in partial response in 3 patients, one of them also achieved long-term disease stabilization with bevacizumab maintenance with no adverse event. Two of the patients had clear benefit from pazopanib during the course of disease. One patient was treated with thalidomide for 18 months with stable disease, and is still being followed without any treatment. Although targeting VEGF-VEGFR pathway seems to be the best approach in HEHE, randomized studies are urgently needed to support these findings.

Prognostic Value of Metabolic Tumor Volume Measured by 18F-FDG PET/CT in Esophageal Cancer Patients.

OBJECTIVE: In this study, we aimed to explore prognostic importance of definition of preoperative metabolic tumor volume in esophageal cancer patients. METHODS: 22 patients who have histologically proven stage IIA-III esophageal cancer and underwent (18)F-FDG PET/CT for preoperative staging of disease were included to the study. After (18)F-FDG PET/CT, all the patients underwent surgery within 4 weeks period. Patients have been followed up until death or Sept 15(th), 2012. Dates of death were recorded for survival analysis. During evaluation of (18)F-FDG PET/CT images, metabolic tumor volumes were calculated by drawing the isocontour region of interests from all visually positive FGD uptake lesions. RESULTS: 22 patients (15M, 7F; mean age: 65.1±8.4, min-max:48-80) underwent (18)F-FDG PET/CT for preoperative staging of esophageal cancer. Preoperative diagnosis was squamous cell and adeno cancer in 17 (%77) and 5 (%23) patients, respectively. Location of primary tumor is distal, proximal and mid-esophagus in 13 (%59), 6 (%27) and 3 (%13) patients, respectively. Primary tumor of all the patients were FDG avid (mean SUVmax: 18.85±7.0; range: 5.5-35.1). Additionally, (18)F-FDG uptake was seen in mediastinal lymph nodes in 13 patients (5.45±8.15; range: 2.6-29.9). Mean metabolic tumor volumes of primary esophageal lesions were calculated as 8.77±8.46cm(3) (range: 2.3-34.2). Mean MTV of lymph nodes was 2.44±1.01cm(3) (range: 0.4-3.6). Mean total metabolic tumor volume was calculated as 9.99±8.58cm(3) (range: 2.3-27.3). 10 patients died during 447±121 days follow-up period. Mean survival time was 11.9±1.5 months (95%CI: 8.99-14.74) for entire patient group. Total metabolic tumor volume had a significant effect on survival (p=0.045) according to Cox proportional hazards regression analysis. One unit increase in MTV caused 1.1 (95%CI:1.003-1.196) fold increase in hazard, at any time. CONCLUSION: Definition of preoperative metabolic tumor volume has a prognostic value in the prediction of postoperative survival times. Patients who have higher preoperative metabolic tumor volumes could be good candidates for more aggressive chemo-radiation therapy regiments. CONFLICT OF INTEREST: None declared.

Oesophageal achalasia misdiagnosed as uncontrolled asthma.

Achalasia is characterized by incomplete lower oesophageal sphincter relaxation and aperistalsis of the oesophagus. It may present with dyspnea symptom. An 18-years-old male patient applied to a clinic with the complaints of cough, dyspnea, wheezing and diagnosed as asthma. Although his asthma treatment was increased in time while he did not recover, he was reffered to our hospital with the diagnosis of uncontrolled asthma. On chest X-ray there was a mild upper mediastinal enlargement and chest computed tomography revealed an over-dilated oesophagus constricting the trachea. The patient was referred to chest surgery clinic with a suspected diagnosis of achalasia. Barium-oesophagogram and endoscopic evaluation of the oesophagus confirmed the diagnosis of achalasia. The patient underwent Heller myotomy and oesophagogastrostomy. He was recovered in one week after the surgery without any complaint of dyspnea. Spirometry tests and chest X-ray resulted normal in one year. With this case of achalasia who used asthma treatment unnecessarily,we wanted to emphasize the importance of differential diagnosis of difficult asthma.

Benign localized fibrous tumor of the pleura: report of 25 new cases.

OBJECTIVE: Benign localized fibrous tumors (BLFT) of the pleura are very rare slow-growing neoplasms that generally have a favorable prognosis. The aim of this manuscript is to evaluate the predictors of outcome with the review of the literature in a series of 25 patients with BLFT. METHODS: Between January 1985 and November 2009, 25 patients underwent an operation due to BLFT. Of these patients, 14 (56%) were male; mean age was 41.1 (25 to 64) years. All patients underwent thoracotomy. Left thoracotomy approach was used in 16 patients. The mass lesions were totally excised. The histopathological examinations were performed with hematoxylin-eosin and immunohistochemical staining methods. RESULTS: Of the patients, 18 (72%) were symptomatic. Symptoms were cough in 36%, shortness of breath in 32%, and chest pain in 20% of the patients. One patient (4%) appeared to have some symptoms (pain and swelling of the joints) associated with pulmonary osteoarthropathy. Seven patients (28%) underwent an operation due to mass lesion detected at routine control visits. None of the patients had a history of exposure to asbestos. Radiological investigations revealed 16 (64%) mass lesions in the left. Of the lesions found on exploration, 5 (20%) were intrapulmonary localized lesion without pedicle and 20 were pedicled. Of the pedicled masses, 5 were connected to parietal pleura and 15 to visceral pleura and all were intrathoracic extrapulmonary localized lesions. Eight (32%) lesions connected to left lower lobe. Additionally, three pedicled lesions were located in the lung fissure. Pedicled lesions were totally excised together with their pedicles. Intraparenchymal mass lesions were resected using wedge resection. The diameter of the resected masses was ranging between 3 and 22 cm (mean: 8.7). Macroscopically, all were encapsulated with a homogeneous cut surface. Intraoperative mortality and morbidity was not observed. The average hospitalization duration for all patients was 8.6 days (5 to 12). The mean follow-up was 33.6 (9 to 142) months with no recurrence. CONCLUSIONS: Benign localized fibrous tumors are uncommon and treated by surgical means. According to our data obtained from literature review, clinicians should be aware of recurrence possibility even after complete resection of benign localized fibrous tumor and the risk of malign transformation.

The coexistence of thymic carcinoma and multiple granulomas in a Turkish child.

Thymic carcinoma, which is a thymic epithelial neoplasm with obvious cytologic atypia, is a rare neoplasm. The authors report on a 10-year-old boy who presented with respiratory distress due to bulky anterior mediastinal mass. Histological and immunohistochemical studies confirmed a lymphoepithelioma-like pattern thymic carcinoma. In addition, evaluation of the specimen showed foci of caseation and multiple granulomas with extensive central necrosis within the thymic tissue. The child received chemotherapy, followed by surgery and radiotherapy. To rule out difficulties of tuberculosis he also received antituberculosis therapy. Two years after cessation of treatment, he is still in remission for thymic carcinoma.

Swallowing of a dynamic tracheal stent: an unusual complication.

Cicatricial tracheal stenoses are mainly related to iatrogenic injury as postintubation, posttracheotomy or postoperative. Advances in airway prosthetics have provided a variety of silicone stents and expandable metal stents as a therapeutic option for tracheal stenoses. Nowadays, dynamic tracheal stents are performed prevalently for the treatment of tracheal stenosis. Four major problems are currently associated with airway stents: Mucostasis, formation of granulation tissue, infection and migration. In this report, we present a case of swallowing a tracheal dynamic stent as an unusual complication of tracheal stents.

Comparison of mersilene mesh-methyl metacrylate sandwich and polytetrafluoroethylene grafts for chest wall reconstruction.

We report the outcomes of patients who underwent reconstruction with Mersilene mesh-methyl methacrylate (MM-MM) sandwich and polytetrafluoroethylene (PTFE) grafts after a large chest wall resection. Between June 1990 and September 2001, 59 consecutive patients (37 men, 22 women; mean age, 48.1 +/- 11.8 years; range 22-74 years) underwent large chest wall resection (greater than 5 cm diameter) and reconstruction with prosthetic material in our department. Twenty-one patients (33%) underwent reconstruction with a PTFE graft (group 2) between 1990 and 1994, and 38 patients (67%) underwent reconstruction with an MM-MM sandwich graft (group 1) between 1994 and 2001. Operative morbidity ratios were 5.2% (2/38) in group 1 and 24% (5/21) in group 2 (p = .036). The paradoxical respiration ratio was significantly higher (p = .018) in group 2 (5/21: 24%) than it was in group 1 (1/38: 2.6%). The operative mortality ratio was 4.5% (1/21) in group 2 and 0% in group 1. Mean hospital stay was 10.6 days (range 5-21 days) in group 1 and 13.3 days (range 7-36 days) in group 2 (p = .015). The MM-MM graft is inexpensive and easy to apply, provides better cosmetic options, and offers minimal morbidity. We therefore recommend that the MM-MM sandwich graft be used rather than the PTFE graft for large defects of the anterolateral chest wall and sternum where successful prevention of paradoxical respiration is required.

Parenchyma-preserving surgery in the management of pulmonary hydatid cysts.

Pulmonary hydatid cysts remain a significant health problem in endemic regions like Turkey. Here, we present our surgical experience in patients with pulmonary hydatid cysts. Between January 1985 and January 2001, 1118 operations were performed in 1032 patients (528 males, 504 females; mean age 32.7 years; range 1-87 years) with pulmonary hydatid cysts in our department. Posterolateral thoracotomy was performed in 1015 (98.3%), two-stage thoracotomy in 34 (3.3%), and median sternotomy in 17 (1.7%) patients. We preferred conservative surgical procedures. As a surgical procedure, cystotomy and capitonnage was performed in 626 (56%), cystotomy alone in 368 (33%), wedge resection in 81 (7%), enucleation in 29 (3%), and decortication in 11 (1%) patients. None of our patients were treated with anatomic resection. During surgery, 949 patients (92%) had unruptured and 83 patients (8%) had ruptured hydatid cyst. The morbidity ratio was 6.7%. Major complications were wound infection (2.3%), prolonged air leak (1.9%), atelectasis (1.2%), pleural effusion (0.8%), postoperative hemothorax (0.6%), and empyema (0.3%). Two patients (0.2%) died within the first month postoperatively. Mean follow-up was 31.2 months. Recurrence was detected in only 35 patients (3.3%). Treatment of pulmonary hydatid cyst is primarily surgical. Medical treatment is indicated for recurrent and multiple hydatid cysts postoperatively. Cystotomy alone, or cystotomy and capitonnage, as parenchyma-preserving surgery, is preferred. Radical surgery including pneumonectomy, lobectomy, and segmentectomy should be avoided.

Single-stage transthoracic approach for right lung and liver hydatid disease.

OBJECTIVE: Human echinococcosis remains a serious health problem for the Mediterranean countries. Synchronous pulmonary and hepatic hydatid disease may occur in 4% to 25% of cases. Our experience on simultaneous surgical treatment of right lung and liver hydatid disease in patients was reviewed. METHODS: Between 1990 and 2000, 48 patients (33 female patients and 15 male patients) with synchronous right lung and liver dome hydatid cysts were operated with a 1-stage procedure. RESULTS: Six patients had previous surgical treatment of hepatic (n = 2) or pulmonary (n = 4) hydatid cyst. The pulmonary cysts were diagnosed with radiography in 18 patients and thoracic computed tomography scan in 30. The pulmonary cysts of 9 patients were bilateral. Seventy-five pulmonary cysts were seen in radiological examinations. The diagnosis of hepatic cysts was established with ultrasonography in 18 patients and upper abdominal computed tomography in 30. The total number of hepatic cysts was 48. In cases with pulmonary cysts, cystotomy and capitonnage were performed in 32 patients, only cystotomy was done in 14 patients, and wedge resection was performed in 2. Liver cysts were approached to transdiaphragmatically after the lung cysts had been dealt with and were managed with evacuation of the cysts. In the remaining cases, marsupialization (n = 2), pericystectomy (n = 1), and enucleation (n = 1) were performed. Major postoperative complications were hemorrhage (n = 1) and biliocutaneous fistula (n = 1). Hepatic recurrence was seen in 3 patients (6.2%) and pulmonary recurrence in 1 (2.1%). CONCLUSION: Transthoracic approach is a useful and a safe surgical management of both pulmonary and upper surface of hepatic hydatid cysts.

Surgical treatment of peripheral lung cancer adherent to the parietal pleura.

OBJECTIVES: The objective of this paper is to assess the results of surgical treatment retrospectively in a consecutive series of 85 patients with peripheral non-small cell lung cancer (NSCLC) invading parietal pleura and chest wall. METHODS: From 1994 to 1998, of the 572 patients having pulmonary resection for NSCLC, 29 patients with neoplasm involving the parietal pleura (group I) and 56 with that invading the chest wall (group II) underwent resection. RESULTS: The operative mortality rate was 3.4% in group I and 1.8% in group II. In groups I and II, pathologic N status was N0 in 20 (69%) cases, N1 in five (17%), N2 in four (13.8%) and 44 (78.6%), seven (12.5%), five (8.9%), respectively. An incomplete resection (R1) was performed in two (6.9%) patients in group I and seven (12.5%) in group II. Postoperative radiotherapy was carried out in 18 patients in group I and 46 in group II. Systemic chemotherapy was also administered in seven patients in group I and eight in group II. There was a significant difference in adjuvant therapy between the groups (P<0.05). Two patients (R1) in group I (7.4%) and 12 patients (seven patients R1+5 R0) in group II (24%) had local recurrence. There was no significant difference in local recurrence between the groups (P=12). Follow-up was completed in 79 cases (28 in group I and 51 in group II). Median survival for groups I and II were 27+/-6 and 16+/-4.6 months, respectively. Five-year survival was longer in group I than in group II (33 vs. 14%), but there was no significant difference (P=13). CONCLUSIONS: We found similar survival rates for extrapleural resection in limited parietal pleura invasion and chest wall resection in exceeded-beyond-parietal pleura invasion. The completeness of resection is important in both groups.

An unusual foreign body in the esophagus: report of a case.

Foreign body ingestion occurs commonly in children and in specific high-risk groups of adults. Foreign bodies in the gastrointestinal tract can result in serious complications depending on the size and shape of the ingested object. This report presents a patient with an unusual foreign body in the esophagus.