Access to Radiation Therapy by Syrian Refugees Displaced to Turkey.

For over 10 years, the Syrian conflict has caused millions of people to leave their homeland, causing one of the biggest refugee crises in modern history. Considering its prevalence, cancer is an important care burden among Syrian refugees. Radiation therapy is one of the essential parts of cancer treatment, and radiation oncology departments must guarantee optimal cancer treatments even in such a challenging setting when patients are displaced forcefully from their homes. National and institutional measures are highlighted in this manuscript to provide suggestions for the delivery of care during refugee crises. There are two issues creating barriers to serving refugee populations: the loss of access to their original care records in Syria for those with a previous diagnosis of cancer referred for continuation of radiation therapy or reirradiation, and the effect of acute radiation therapy toxicity on treatment compliance.

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.

Serum nectin-2 and nectin-4 are diagnostic in lung cancer: which is superior?

Nectins are immunoglobulin-like molecules that are involved in cell to cell adhesion by forming tight junctions and homophilic/heterophilic interactions. This study aimed to analyze serum nectin­2 and nectin­4 levels in lung cancer patients and to evaluate the prognostic, diagnostic and predictive strengths. Data from 74 lung cancer patients were retrospectively examined and enzyme-linked immunosorbent assays (ELISA) were used to measure serum nectin­2 and nectin­4 concentrations. A total number of 40 age and sex-adjusted healthy controls were also enrolled in the study. The median serum nectin­2 and nectin­4 levels of the patients were significantly higher than those of controls (p < 0.001); however, neither biomarker was found to be associated with clinicopathological parameters, (p > 0.05), and furthermore they were found not to be correlated with either overall survival or progression-free survival (p > 0.05). Even though both markers showed high diagnostic values, serum nectin­2 was found superior to both serum nectin­4 and serum nectin-2 + nectin­4 combinations in the diagnosis of lung cancer according to higher sensitivity, specificity and predictive values. Serum nectin­2 and nectin­4 might be used in lung cancer diagnosis but the diagnostic importance of nectin­2 is higher. The prognostic and predictive strengths in cancer are controversial. Furthermore, the interactions with tumor microenvironments and the potentials as therapeutic targets for malignancies have yet to be elucidated.

The expression level of fibulin-2 in the circulating RNA (ctRNA) of epithelial tumor cells of peripheral blood and tumor tissue of patients with metastatic lung cancer.

The Fibulins are a recently discovered family of extracellular matrix proteins. In this study, expression levels of the fibulin-2 (FBLN2) gene and its role in the formation of different metastatic foci were investigated in lung cancer patients. We analyzed 106 lung cancer patients and eight paraffin-embedded tissues, and 27 ethnical-, age- and sex-matched healthy controls for expression levels of the FBLN2 gene. cDNAs obtained from the enriched epithelial cells of peripheral blood lymphocytes and tumor tissues of patients were amplified with specific primers for the target FBLN2 gene and HPRT1 housekeeping gene using quantitative real-time polymerase chain reaction. FBLN2 gene expression levels of the enriched epithelial cells of peripheral blood lymphocytes were found to be decreased approximately twofold in all subsets of patients compared to healthy controls. Our results indicate a significant difference between patient subgroups and controls [F(4.124) = 14.846, p0.05] among patient subgroups: bone metastases versus non-metastatic groups (p = 0.997), bone versus brain metastases (p = 0994), bone metastases versus two primary tumors (p = 0.999), brain metastases versus two primary tumors (p = 0.999), brain metastases versus non-metastatic (p = 0.755), non-metastatic versus two primary tumors (p = 0.996), non-metastatic versus all other metastatic patients (p = 0.731). Moreover, we found a 50-fold upregulation of FBLN2 gene expression in paraffin-embedded tissues compared with the enriched epithelial cells of peripheral blood lymphocytes of patients. In the study, the enriched epithelial cells of peripheral blood lymphocytes of decreased FBLN2 expression was found to be correlated with metastasis. The fibulin-2 molecules might induce the metastatic potential through interaction with the other molecules in the microenvironment, nevertheless, it is needed further research whether the importance of FBLN2 on lung cancer oncogenesis and as a biomarker for metastatic lung cancer.

Abscopal Effect of Radiotherapy in the Immunotherapy Era: Systematic Review of Reported Cases.

Mounting evidence suggests that radiation stimulates the immune system and this contributes to the abscopal effect, which is defined as "response at a distance from the irradiated volume." Though identified more than 50 years ago, the abscopal effect is revisited today. One rationale is that the abscopal effect is often observed with efficient immunotherapy. Here, we give an overview of the clinical data on the abscopal effect, generated by a combination of immunotherapy and radiotherapy (RT). Only papers that included RT in combination with immunotherapy were evaluated according to four main categories including RT parameters, sequencing of therapies, the definition of the abscopal effect, and patient selection. Twenty-four cases in 15 reports were reviewed. The results varied. Patient ages ranged from 24 to 74. RT dose (median total dose 18-58 Gy) varied. Biologically effective dose (BED) 10 was calculated to be a median 49.65 Gy (28-151 Gy). The time to a documented abscopal response ranged from less than a month to 12 months. The large variation concerning fractionation and sequencing of therapies indicates that these conflicting points need to be resolved, to generate for the abscopal effect to be clinically significant.

Circulating interleukin-18 (IL-18) is a predictor of response to gemcitabine based chemotherapy in patients with pancreatic adenocarcinoma.

BACKGROUND: This study was conducted to investigate the serum levels of interleukin-18 (IL-18) in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters. METHODS: Thirty-three patients with PA were studied. Serum samples were obtained on first admission before any treatment. Serum IL-18 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 30 healthy controls were included in the analysis. RESULTS: The median age at diagnosis was 59 years, range 32-84 years; 20 (61%) patients were men and the remaining were women. The median follow-up time was 26.0 weeks (range: 1.0-184.0 weeks). The median overall survival of the whole group was 41.3 ± 8.3 weeks [95% confidence interval (CI) = 25-58 weeks]. The baseline serum IL-18 levels were significantly higher in patients with PA than in the control group (p < 0.001). Serum IL-18 levels were significantly higher in the patients with high erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) (p = 0.01 and p = 0.05). Moreover, the chemotherapy-(CTx) unresponsive patients had higher serum IL-18 levels compared to CTx-responsive (p = 0.04) subjects. Conversely, serum IL-18 concentration was found to have no prognostic role on survival (p = 0.45). CONCLUSION: Serum levels of IL-18 can be a good diagnostic and predictive marker; especially for predicting the response to gemcitabine based CTx in patients with PA but it has no prognostic role.

Post operative stereotactic radiosurgery for positive or close margins after preoperative chemoradiation and surgery for rectal cancer.

BACKGROUND: The incidence of positive margins after neoadjuvant chemoradiation and adequate surgery is very low. However, when patients do present with positive or close margins, they are at a risk of local failure and local therapy options are limited. We evaluated the role of stereotactic body radiotherapy (SBRT) in patients with positive or close margins after induction chemoradiation and total mesorectal excision. METHODS: This is a retrospective evaluation of patients treated with SBRT after induction chemoradiation and surgery for positive or close margins. Seven evaluable patients were included. Fiducial seeds were place at surgery. The Cyberknife(TM) system was used for planning and treatment. Patients were followed 1 month after treatment and 3-6 months thereafter. Descriptive statistics and Kaplan-Meir method was used to repot the findings. RESULTS: Seven patients (3 men and 4 women) were included in the study with a median follow-up of 23.5 months. The median initial radiation dose was 5,040 cGy (in 28 fractions) and the median SBRT dose was 2,500 cGy (in 5 fractions). The local control at 2 years was 100%. The overall survival at 1 and 2 years was 100% and 71% respectively. There was no Grade III or IV toxicity. CONCLUSIONS: SBRT reirradiation is an effective and safe method to address positive or close margins after neoadjuvant chemoradiation and surgery for rectal cancer.

Stereotactic Body Radiotherapy (SBRT) Reirradiation for Recurrent Pancreas Cancer.

OBJECTIVES: After adjuvant or definitive radiation for pancreas cancer, there are limited conventional treatment options for recurrent pancreas cancer. We explored the role of (Stereotactic Body Radiotherapy) SBRT for reirradiation of recurrent pancreas Cancer. METHODS: This is a retrospective study of patients reirradiated with SBRT for recurrent pancreas cancer. All patients were deemed unresectable and treated with systemic therapy. Fiducial gold markers were used. CT simulation was performed with oral and IV contrast and patients were treated with respiratory motion tracking in the Cyberknife(TM) system. RESULTS: 30 patients (17 men and 13 women) with a median age of 67 years were included in the study. The median target volume was 41.29cc. The median prescription dose was 25Gy (24-36Gy) in a median of 5 fractions prescribed to a mean 78% isodose line. The median overall survival was 14 months. The 1 and 2 year local control was 78%. The worst toxicity included 3/30(10%) Grade III acute toxicity for pain, bleeding and vomiting. There was 2/30 (7%) Grade III long-term bowel obstructions. CONCLUSIONS: SBRT can be a useful and tolerable option for patients with recurrent pancreas cancer after prior radiation.

Turkish Ministry of Health, 2nd Turkish Medical General Assembly Clinical Oncology Study Group Report.

OBJECTIVE: There is an increase in the incidence of cancer, and consequently in mortality rates, both in the world and in Turkey. The increase in the incidence and mortality rate of cancer are more prominent in our country as well as in other developing countries. The aim of this workshop was to determine the current status on prevention, screening, early diagnosis and treatment of cancer in our country, to identify related shortcomings, specify solutions and to share these with health system operators, and to aid in implementation of these systems. Developments on palliative care were also evaluated. MATERIALS AND METHODS: The current situation in the practice of clinical oncology, related drawbacks, problems encountered during multidisciplinary approach and their solutions were discussed under several sub-headings during a 3-day meeting organized by the Turkish Ministry of Health (Türkiye Cumhuriyeti Saglik Bakanligi-TCSB) with participation of 16 scientists from Turkey and 6 from abroad, and the conclusions were reported. RESULTS: It is expected that the newly established Turkish Health Institutes Association (Türkiye Saglik Enstitüleri Baskanligi-TÜSEB) and the National Cancer Institute (Ulusal Kanser Enstitüsü) will provide a new framework in the field of oncology. The current positive findings include the increase in the number of scientists who carry out successful trials in oncology both in Turkey and abroad, the implementation of the national cancer registry program by the Cancer Control Department and the breast cancer registry program by the Turkish Federation of Breast Diseases Societies (Türkiye Meme Hastaliklari Dernekleri Federasyonu-TMHDF), and introduction of Cancer Early Diagnosis, Screening, and Training Centers (Kanser Erken Tani, Tarama ve Egitim Merkezi-KETEM) for the application of community-based cancer screening programs. In addition to these, obvious shortcomings related to education, implementation, management and research issues were also determined, and policy and project proposals to address these issues were presented. Collaboration with relevant organizations in the implementation of these studies was supported. CONCLUSION: Both the incidence and mortality rates of cancer are increasing in Turkey. The widespread deficiencies in population-based screening and in effective treatment lead to an increase in delay in diagnosis and mortality. Despite improvements in data recording, screening and treatment over the last 10 years, extensive, organized, population-based screening programs and fully equipped early diagnosis and treatment centers are required. Enhancement of basic cancer epidemiologic, translational, genetic and molecular research studies is essential in our country. Improvements on pain treatment and palliative care of patients with chronic and terminal cancer are also required.

Stereotactic Body Radiotherapy (SBRT) for Intrahepatic and Hilar Cholangiocarcinoma.

BACKGROUND: Unresectable intrahepatic and hilar cholangiocarcinomas carry a dismal prognosis. Systemic chemotherapy and conventional external beam radiation and brachytherapy have been used with limited success. We explored the use of stereotactic body radiotherapy (SBRT) for these patients. METHODS: Patients with unresectable intrahepatic or hilar cholangiocarcinoma or those with positive margins were included in this study. Systemic therapy was used at the discretion of the medical oncologist. The Cyberknife(TM) stereotactic body radiotherapy system used to treat these patients. Patients were treated with three daily fractions. Clinical and radiological follow-up were performed every three months. RESULTS: 34 patients (16 male and 18 female) with 42 lesions were included in this study. There were 32 unresectable tumors and two patients with resected tumors with positive margins. The median SBRT dose was 30Gy in three fractions. The median follow-up was 38 months (range 8-71 months). The actuarial local control rate was 79%. The median overall survival was 17 months and the median progression free survival was ten months. There were four Grade III toxicities (12%), including duodenal ulceration, cholangitis and liver abscess. CONCLUSIONS: SBRT is an effective and reasonably safe local therapy option for unresectable intrahepatic or hilar cholangiocarcinoma.

Therapeutic Potential of Adjuvant Stereotactic Body Radiotherapy for Gallbladder Cancer.

Surgical treatment remains the only curative treatment for gallbladder cancer. However, even after liver resection, locoregional failure seems to be a significant problem. While there is no Level I evidence, multiple studies have shown benefit for adjuvant radiation in high-risk patients. After extensive liver resection, tolerance to conventional chemoradiation may be limited by potential liver toxicity. Stereotactic body radiotherapy has been used safely and effectively in hepatobiliary malignancies. We present a case report, highlighting the potential therapeutic role of adjuvant stereotactic body radiotherapy (SBRT) for gallbladder cancer.

Radiation Therapy in the Management of Malignant Melanoma.

The initial treatment for primary and locoregional melanoma is surgery. Systemic therapy, and more recently immune therapy, has been the mainstay in the adjuvant and particularly the metastatic setting. Aside from palliation, there is a limited role for definitive radiation therapy for melanoma. However, in the adjuvant setting, postoperative radiation can improve locoregional disease control, albeit with potential toxicity and limited survival benefit. Stereotactic radiosurgery plays a vital role in the treatment of limited brain and extracranial metastasis.

Stereotactic body radiotherapy (SBRT) reirradiation for pelvic recurrence from colorectal cancer.

BACKGROUND AND OBJECTIVES: When surgery is not adequate or feasible, stereotactic body radiotherapy (SBRT) reirradiation has been used for recurrent cancers. We report the outcomes of a series of patients with pelvic recurrences from colorectal cancer reirradiated with SBRT. METHODS: The Cyberknife(TM) Robotic Stereotactic Radiosurgery system with fiducial based real time tracking was used. Patients were followed with imaging of the pelvis. RESULTS: Four women and 14 men with 22 lesions were included. The mean dose was 25 Gy in median of five fractions. The mean prescription isodose was 77%, with a median maximum dose of 32.87 Gy. There were two local failures, with a crude local control rate of 89%. The median overall survival was 43 months. One patient had small bowel perforation and required surgery (Grade IV), two patients had symptomatic neuropathy (1 Grade III) and one patient developed hydronephrosis from ureteric fibrosis requiring a stent (Grade III). CONCLUSIONS: Local recurrence in the pelvis after modern combined modality treatment for colorectal cancer is rare. However it presents a therapeutic dilemma when it occurs; often symptomatic and eventually life threatening. SBRT can be a useful non-surgical modality to control pelvic recurrences after prior radiation for colorectal cancer.

The role of colorectal stent placement in the management of acute malignant obstruction.

BACKGROUND: In recent decades, the use of colorectal stents for palliation or as a bridge to surgery in acute malignant colorectal obstruction has increased. We aimed to evaluate the technical and clinical efficacy, safety and clinical outcomes of endoscopic stenting for the relief of acute colorectal obstruction secondary to cancer. METHODS: From March 2006 to December 2012, among 100 patients with acute malignant colorectal obstruction, stenting procedures were performed on 42 patients for relief of obstruction. Uncovered self-expanding metal stents (SEMS) were placed endoscopically under fluoroscopic guidance in all patients. Using the patient database, a review was conducted to determine the effectiveness of the procedure and the short- and long-term complications. RESULTS: Stent placement was technically successful in 39/42 (92.8%) and clinically successful in 38/42 (90.4%) patients. Sixteen patients later underwent an elective surgical resection, and in 26 patients with metastatic disease or comorbidity, stent placement was palliative. Complications occurred in 10 (23.8%) patients, and the most common was tenesmus (n=3). Migration, bleeding, and recto-sigmoid perforation occurred in two patients each. Stent obstruction due to fecal impaction was seen in one case. CONCLUSION: Stent placement for colorectal obstruction is an effective and relatively safe procedure, with minor complications. It not only allows subsequent elective resection, but is also definitive for palliative treatment in patients with obstructive colorectal cancer.

Definitive radiotherapy in locally advanced non-small cell lung cancer: dose and fractionation.

Definitive radiotherapy plays a major role in the treatment of locally advanced non-small cell lung cancer (LA NSCLC). After the impact of RT dose for lung cancer was established, a number of trials were structured with the aim of better local control and overall survival by either dose escalation or shortening the total treatment time through conventional/altered fractionation, even in combination with chemotherapy (CT) and other targeted agents. In spite of the increased number of these studies, the optimal dose or fractionation still remains to be determined. Another aspect questioned is the incorporation of these higher doses and shorter treatment times with chemotherapy or targeted agents. This review summarises the results of significant trials on dose and altered fractionation in the treatment of LA-NSCLC with an emphasis on possible future perspectives.

Noncutaneous melanoma have distinct features from each other and cutaneous melanoma.

OBJECTIVE: Compared to the cutaneous melanoma, noncutaneous melanomas are relatively rare and have a distinct pattern of behavior. We performed this study to define the clinical characteristics and outcomes of patients with noncutaneous melanomas and emphasize how they differ from cutaneous melanomas. METHODS: 216 patients who were diagnosed with noncutaneous melanoma were assessed and their medical records between 2000 and 2010 were retrieved from the cancer registry. 475 patients with cutaneous melanoma were used for comparison. RESULTS: Of the 216 noncutaneous melanoma patients, 83 had mucosal melanoma, 101 had ocular melanoma and 32 had unknown primaries. For mucosal melanoma, the head and neck was the most common anatomic site (53%), followed by the gastrointestinal tract (37%), female genital (6%) and urinary tract (4%). The majority of the ocular melanomas (94%) originated in the uvea. 32 patients demonstrated a primary unknown disease with regional metastasis as the dominant behavior (72%). Age was found to be statistically significantly different among melanoma patients (p < 0.001). Younger patients had more cutaneous and unknown primary melanomas, whereas older patients had more ocular and mucosal melanoma. In subset analyses, we found significant differences between cutaneous and ocular (p = 0.038) or mucosal (p < 0.001) melanomas. The ratios of metastasis on admission were higher in patients with mucosal (27.7%) and unknown primary (28.1%) melanomas, and lower for ocular (3%) melanomas (p < 0.001). Patients with cutaneous melanoma had an intermediate (12%) ratio. Patients with ocular melanoma had better outcome than patients with other melanoma sites (p < 0.05). While overall survival for cutaneous melanoma was significantly negatively correlated with male gender (p < 0.001), advanced stages (p < 0.001) and old age (p = 0.005), stage IV disease was the only independent prognostic factor in patients with ocular melanoma (p = 0.006). No prognostic factor for outcome was found for either mucosal or unknown primary melanomas. CONCLUSION: The clinical presentations and prognoses of different primary sites of melanoma are distinctive. Therefore, approaches to these melanomas should be different.

Surgical treatment and prognosis of primitive neuroectodermal tumors of the thorax.

INTRODUCTION: Primitive neuroectodermal tumors (PNETs) are rare, rapidly progressive, small- round cell tumors with a poor prognosis despite multimodal therapy, including surgery and chemoradiotherapy. The treatment of choice was unknown since no clinical series with surgical therapy had been reported. We evaluated the impact of multimodal treatment in patients with PNETs located in the thoracic region. METHODS: Between 1998 and 2006, 25 patients with PNETs in the thoracic region were treated in 3 tertiary-care hospitals. The patients consisted of 15 males and 10 females with a mean age of 27.2 years (range, 6-60). The tumor was in the chest wall in 20 (involving the costovertebral junction in 9), the lung in four, and the heart in one patient. Twelve patients received neoadjuvant chemotherapy (54.5%), and 22 of 25 patients underwent surgery. RESULTS: In patients who received neoadjuvant treatment, the mean regression rate was 65.4% (range, 30-100%). Eighteen (82%) patients underwent chest wall resection, while 7 (32%) had vertebral resections, and the remaining 4 (16%) had pulmonary resections. A complete resection was possible in 18 of 22 patients (82%). Patients with incomplete and complete resections had 25% and 56% 5-year survival rates, respectively (p = 0.13). The progression-free 3-year survival rate was 36% and the median survival time was 13 months. The complete resection rate was significantly higher in patients receiving neoadjuvant therapy (p = 0.027). The 5-year survival rate of the patients with or without neoadjuvant therapy was 77% and 37%, respectively (p = 0.22) although it prolonged the disease-free survival (p = 0.01). The 5-year survival rate of patients without costovertebral junction involvement was 66%, whereas patients with PNETs involving the costovertebral junction had a 21% 3-year survival. The difference was statistically significant (p = 0.01). The 5-year progression-free survival rate of patients without costovertebral junction involvement was 58%, whereas patients with PNETs involving the costovertebral junction had a 14% 1-year progression-free survival (p = 0.004). CONCLUSIONS: PNET is an aggressive malignancy that often requires multimodal therapy. Induction chemotherapy leads to a greater complete resection rate and better disease-free survival, while involvement of the costovertebral junction indicates a poorer survival.