Berna Akkus Yildirim

Cranial Prophylactic Irradiation in Locally Advanced Non-Small Cell Lung Carcinoma: Current Status and Future Perspectives

As a result of improved local and regional control with aggressive multimodality protocols, the brain has become one of the major sites of relapse in patients with locally advanced non-small cell lung carcinoma (LA-NSCLC). The demonstrated efficacy of prophylactic cranial irradiation (PCI) in small-cell lung carcinoma led to studies of its effectiveness in LA-NSCLC, which indicated that PCI also has a high potential to reduce the incidence or delay the occurrence of brain metastases in this patient group. This report provides an extensive review of the current evidence from nonrandomized and randomized trials regarding the use of PCI in LA-NSCLC and discusses related key issues including risk factors, patient selection criteria, timing of PCI, preferred PCI dosing scheme, toxicity profile and potential novel PCI techniques.

Prognostic Use of Pretreatment Hematologic Parameters in Patients Receiving Definitive Chemoradiotherapy for Cervical Cancer.

Objectives The aim of this work was to evaluate the prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in recipients of definitive chemoradiotherapy (ChRT) for cervical cancer. Methods In 235 patients given definitive ChRT for histologically confirmed cervical cancer, clinical data and pretreatment complete blood cell counts were analyzed. Prognostic and therapeutic ramifications of NLR and PLR were assessed. Results Median pretreatment NLR and PLR were 3.03 (range, 1.04–13.03) and 133.02 (range, 36.3–518.16), respectively. Both NLR and PLR correlated significantly with tumor size, lymph node metastasis, and treatment response. In addition to NLR and PLR, tumor stage, size, and nodal metastasis were identified by univariate analysis as significant predictors of overall survival (OS) and progression-free survival (PFS). By multivariate analysis, independent predictors of OS and PFS were NLR (OS: hazard ratio [HR], 3.322; 95% confidence interval [CI], 1.905–5.790; PFS: HR, 3.579; 95% CI, 2.106–6.082; both P < 0.001) and lymph node metastasis (OS: HR, 2.620; 95% CI, 1.706–4.023; PFS: HR, 2.989; 95% CI, 1.918–4.378; both P < 0.001), although patients’ age (HR, 1.019; 95% CI, 1.003–1.035; P = 0.02) was also significantly predictive of OS. Conclusions Pretreatment NLR and PLR were associated with larger tumors, lymph node metastasis, and poorer therapeutic responses to definitive ChRT. By multivariate analysis, pretreatment NLR and lymph node metastasis were found independently predictive of OS and PFS, whereas patients’ age was significantly predictive of OS only. In patients with advanced cervical cancer, NLR is a potential biomarker, serving to guide systemic therapy and predict treatment outcomes.

Prognostic value of metabolic response measured by 18F-FDG-PET in oesophageal cancer patients treated with definitive chemoradiotherapy.

BackgroundThis study aimed to assess the efficacy of fluorine-18 fluorodeoxyglucose (18F-FDG)-PET for predicting overall survival (OS) and disease-free survival (DFS) in oesophageal cancer patients after definitive chemoradiotherapy (CRT) and prognostic importance of metabolic response detected by post-treatment PET at least 3 months after completing CRT. Materials and methodsData from 58 oesophageal cancer patients receiving definitive CRT were retrospectively analysed. Post-treatment 18F-FDG-PET was delivered at a median of 3.2 (range, 3.0–6.4) months after CRT. The impact of metabolic response determined by post-treatment 18F-FDG-PET, maximum post-treatment standardized uptake value (SUVmax) and percent SUV change (pretreatment to post-treatment) on survival was analysed. ResultsThe median follow-up was 19.7 (range, 4.2–91.9) months for all patients and 28.2 (range, 13.7–91.9) months for survivors. The mean pretreatment and post-treatment SUVmax and the median percent SUV decrease were 18.6±6.4, 6.2±4.6 and –73% (+13 to −100%). Pretreatment SUVmax was higher in patients with locoregional or distant failure than in those without (P<0.001). Pretreatment SUVmax was lower in patients with a complete response (CR) than in those without a CR (P=0.006). Two-year OS and DFS were higher in patients with CR compared with those without CR (P<0.001). CR rates detected by post-treatment 18F-FDG-PET were lower in patients with lymph node metastases or longer tumours than in those with shorter tumours or no metastases. During multivariate analysis, post-treatment SUVmax was a significant predictor for OS, and post-treatment SUVmax, percent SUV decrease and tumour length were significant prognostic factors for DFS. ConclusionMetabolic response assessed by post-treatment 18F-FDG-PET at least 3 months after CRT showed that post-treatment SUVmax and percent SUV change were important survival predictors.

Safety and Palliative Efficacy of Single-Dose 8-Gy Reirradiation for Painful Local Failure in Patients With Stage IV Non-Small Cell Lung Cancer Previously Treated With Radical Chemoradiation Therapy

PURPOSE To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal. PATIENTS AND METHODS We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a ≥2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors. RESULTS Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P<.001) were found to be associated with longer OS. CONCLUSIONS Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans.

Local recurrence outcomes after breast conserving surgery and adjuvant radiotherapy in ductal carcinoma in situ of the breast and a comparison with ECOG E5194 study

PURPOSE Turkish Radiation Oncology Study Group investigated local recurrence rates and prognostic factors in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conservative surgery (BCS) followed by radiotherapy (RT) and Eastern Cooperative Oncology Group (ECOG) Study E5194 were compared with the original study. PATIENTS AND METHODS Totally 252 patients were evaluated retrospectively. Prognostic factors that might influence local control (age, nuclear grade, comedo necrosis, surgical margins, tumor size, hormone receptor status) were compared. The eligibility criteria of ECOG 5194 were stratified into two groups as in the original study and were compared for local control. RESULTS The median follow-up time was 59 (21-220) months. Local recurrence was observed in 9 patients (3.6%) who had invasive carcinoma (3 patients) and DCIS (6 patients). Ten years local control rates was 91.8% respectively. We found that the risk of ipsilateral breast recurrence was significantly higher in women younger than 50 years old (p = 0.016). In addition, a statistically significant trend was found in patients with tumor larger than 1 cm and HER2 positive tumors (p = 0.051, p = 0.068 respectively). When 12-year results were compared with the ECOG 5194, adjuvant RT produced an absolute difference of 11% in low-intermediate and 20% in high grade in local control. CONCLUSION In our study, the 10-year local control rate was 92% and younger than 50 years old was the most important unfavorable prognostic factor for local recurrence. There was provided 20% absolute local control with adjuvant radiotherapy which eligibility criteria of ECOG 5194 high grade group.

Treatment outcomes of breast cancer liver metastasis treated with stereotactic body radiotherapy

BACKGROUND To assess the outcomes of breast cancer liver metastasis (BCLM) treated with stereotactic body radiotherapy (SBRT) and systemic treatment. MATERIALS AND METHODS Patients with oligometastasis at the time of liver metastasis (LM) or who became oligometastatic (≤5 metastases) after systemic treatment were assessed. Twenty-nine liver metastatic lesions were treated with a total of 54 Gy delivered in 3 fractions. The local control (LC), overall survival (OS), and progression-free survival (PFS) rates were calculated using Kaplan-Meier analyses. RESULTS A total of 22 patients with 29 liver metastatic lesions treated with liver SBRT between April 2013 and September 2017 were retrospectively analyzed. After a median follow-up time of 16.0 months (range 4.4-59.4 months), 18 patients (82%) had disease recurrence, median of 7.4 months (range 1.0-27.9 months) after completion of liver SBRT. The 1- and 2-year OS rates were 85% and 57%, and the 1- and 2-year PFS rates were 38% and 8%, respectively. The 1- and 2-year LC rates were 100% and 88%, respectively. No significant prognostic factors, including disease extension, size of metastasis, number of liver metastasis and timing of liver metastasis, hormonal status affecting OS, PFS and LC were found. No patients experienced Grade 4 or 5 toxicity; furthermore, only one patient experienced rib fracture 6 months after completion of treatment, and one patient had a duodenal ulcer. CONCLUSION This study is the first to evaluate the feasibility of SBRT to BCLM patients. Liver SBRT is a conservative approach with excellent LC and limited toxicities.

Chemoradiotherapy-Induced Hemoglobin Nadir Values and Survival in Patients with Stage III Non-Small Cell Lung Cancer

PURPOSE We investigated the influence of change in hemoglobin (Hgb) levels during concurrent chemoradiotherapy (C-CRT) on outcomes of non-anemic patients with stage IIIA/B non-small cell lung cancer (NSCLC). METHODS We identified 722 patients with stage IIIA/B NSCLC without anemia at baseline [hemoglobin (Hgb) <12 g/dL for women or <13 g/dL for men], either nonsmokers or ex-smokers, who received C-CRT between 2007 and 2012. All patients had received 1-3 cycles of platinum-based doublet chemotherapy during radiotherapy to 60-66 Gy and had documented Hgb measurements before treatment and at weekly intervals for 6 weeks during the C-CRT. Potential associations were assessed between baseline, nadir, extent of change in Hgb level, and anemia and overall survival (OS), locoregional progression-free survival (LRPFS), and PFS. RESULTS The median baseline Hgb level was 13.9 g/dL (range 12.0-16.8) and declined to a median 12.4 g/dL (range 7.9-16.1) during treatment. Anemia appeared in 237 patients (32.8%) and was more common among women (44.8% vs. 26.5%, P < 0.001). Neither baseline Hgb level nor change during treatment nor anemia emergence influenced any survival endpoint. Receiver operating curve analysis revealed an Hgb nadir of 11.1 g/dL to be associated with outcomes, in that a nadir Hgb <11.1 g/dL (in 156 patients) was linked with shorter median OS time (P < 0.001), LRPFS time (P < 0.001), and PFS time (P < 0.001); retained significance for all three endpoints in multivariate analyses; and was more strongly associated with OS in squamous cell carcinoma (P < 0.001) than in adenocarcinoma (P = 0.009). CONCLUSION Nadir Hgb <11.1 g/dL levels during C-CRT were associated with significantly poorer survival times in initially non-anemic patients presenting with locally advanced NSCLC.

Prognostic values of ADCmean and SUVmax of the primary tumour in cervical cancer patients treated with definitive chemoradiotherapy

Abstract We analysed the correlation of 18F-fluorodeoxyglucose uptake into primary tumours using the maximum standardised uptake value (SUVmax) and the mean apparent diffusion coefficient (ADCmean) values in magnetic resonance imaging (MRI) with the clinical and pathological factors in patients with cervical cancer who were treated with concurrent chemoradiotherapy. The patients were stratified according to the primary tumour pre-treatment ADCmean and SUVmax cut-off values. There were significant correlations between the SUVmax of the primary tumour and tumour size, and the treatment response. The correlation between the ADCmean and FIGO stage, tumour size, and the lymph node metastasis was significant. The SUVmax was significantly and inversely correlated with the ADCmean for cervical cancer (r = −0.44, p <.001). In the multivariate analysis, the primary tumour ADCmean, treatment response and the lymph node metastasis emerged as significant independent predictors of both OS and DFS, and of the primary tumour SUVmax for DFS. Tumour size has a borderline significance for OS. High SUVmax and low ADCmean of the primary tumour are important predictive factors for identifying high-risk patients with cervical cancer who are treated with definitive chemoradiotherapy. These results point to a future role for the diffusion-weighted MRI and for 18F-fluorodeoxyglucose positron emission tomography, not only in the staging of cervical cancer but as an aid in the selection of an adjuvant treatment regimen after chemoradiotherapy for individual patients. Impact statement What is already known on this subject? A negative correlation between primary tumour SUVmax derived from positron emission tomography (PET/CT) and ADCmin derived from diffusion weighted magnetic resonance imaging (DW-MRI) in various cancer types and cervical cancer has been demonstrated. However, the prognostic value of primary tumour SUVmax and ADCmean in cervical cancer patients treated with definitive chemoradiotherapy is not well studied yet. What the results of this study add? The patients with high-risk features (larger tumours, extensive stage, lymph node metastasis) had higher primary tumour SUVmax and lower ADCmean values. Primary tumour ADCmean and lymph node metastasis emerged as significant independent predictors of both overall and disease-free survival. This study demonstrated that the functional biomarkers delivered from PET-CT and DW-MRI are important in predicting the treatment outcomes in the squamous cell carcinoma of cervix treated with definitive chemoradiotherapy, where clinical and radiological findings are very important, since these patients are not staged surgically. What are the implications of these findings for clinical practice and/or further research? Based on these findings, there may be a future role of DW-MRI and FDG/PET-CT not only in the staging of cervical cancer but as an aid in the selection of an adjuvant treatment regimen after chemoradiotherapy (ChRT) for individual patients.

Adjuvant uzatılmış temozolamid tedavisinin glioblastoma multiforme hastalarının sağkalımına etkisi

Amac: Retrospektif bu calismanin amaci cerrahi/biyopsi ile glioblastoma multiforme tanisi almis, kemoradyoterapi uygulanmis hastalarda uzatilmis temozolamid kullaniminin genel ve progresyonsuz sagkalim etkisini arastirmak olarak belirlendi. Gerec ve Yontem: Klinigimize basvuran cerrahi/biyopsi ile glioblastoma multiforme tanisi almis 225 hastadan, temozolamid ile birlikte radyoterapi tedavisi uygulandiktan sonra, ≤6 ay ve >6 ay sureyle adjuvan temozolamid kemoterapisi uygulanmis 116 hastatedavi toleransi, genel ve progresyonsuz sagkalimlari arasindaki farklar retrospektif olarak incelendi. Bulgular: Hastalarin ortalama takip suresi 18 ay (2-125 ay) olarak belirlenirken, 65(%56) hasta halen hayattadir. Uzatilmis temozolamid (>6 ay) olan grupta genel sagkalim daha uzun tespit edilirken istatistiksel bir fark tek degiskenli analizde tespit edilememistir sirasiyla 49.0 (≤6)vs 68.33 ay(>6). Ancak progresyonsuz sagkalim suresi uzatilmis temozolamid grubunda standart temozolamid alan gruba gore istatistiksel olarak anlamli oranda uzun saptanmistir 14 (>6)vs 9 ay(≤6). Gruplar arasinda anlamli bir yan etki farkliligi gorulmemistir. Sonuc: Calismamizda glioblastoma multiforme tanisi almis hastalarda uzatilmis temozolamid kullanimi hastalarin progresyonsuz sagkalim ve genel sagkalimlarinin belirgin oranda artmasina neden olur.

Radiotherapy in the Management of Testicular Cancers

Testicular cancers are the most common solid malignancies affecting males between the ages of 15 and 35 years, although it accounts for only about 1% of all cancers in men. Approximately 95% of testicular tumors are germ cell tumors (GCT). At diagnosis, 1–2% of cases are bilateral and 80% of patients are diagnosed at stage I. The risk factors for testicular cancers are family history, cryptorchidism, altered hormonal environment, low fertility, abnormal sperm analysis, and immunosuppression. For treatment purposes, two broad categories are recognized: pure seminoma (no non-seminomatous elements present) and all others, which together are termed non-seminomatous germ cell tumors (NSGCT). Seminoma is highly sensitive to chemotherapy and radiotherapy (RT). The prognosis of patients is generally good; cure is an expected outcome in the majority of cases, even with metastatic disease.