Guler Yavas

Prospective assessment of quality of life and psychological distress in patients with gynecologic malignancy: a 1-year prospective study.

Objective Our aim was to evaluate the health-related quality of life (HRQoL) and psychological distress in patients treated with radiotherapy (RT) for gynecologic malignancy. Methods Fifty-seven women with either cervical or endometrial cancer were prospectively enrolled. We assessed HRQoL at baseline (after surgery before RT), at the end of RT, and during follow-up (every 3 months thereafter) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 24 (EORTC QLQ-CX24), and Hospital Anxiety and Depression Scale. Results We demonstrated changes in appetite loss (P = 0.03), nausea and vomiting (P = 0.02), and role function score (P = 0.003) domains of EORTC QLQ-C30. Only the mean body image score of EORTC QLQ-CX24 was significantly different during follow-up (P = 0.02). Type of surgery, histopathological diagnosis, and the menopausal and marital status of the patients affected baseline body image scores (P = 0.032, 0.004, and 0.019 and 0.005, respectively). Patients who underwent chemotherapy had higher baseline body image scores when compared with patients without any chemotherapy before RT (P = 0.028). All the complaints of patients except body image scores improved during the follow-up period. The baseline and follow-up anxiety and depression scores did not differ significantly. Conclusions Although pelvic RT deteriorated HRQoL in gynecologic cancer, patients’ improvement in HRQoL during follow-up was observed. Patients receiving RT could be reassured about the improvement of acute adverse effects in the course of treatment.

Effect of the percentage of body fat on surgical, clinical and pathological outcomes in women with endometrial cancer

This study used the measure of percentage of body fat (%BF) to define obesity and evaluated the effect of percentage of %BF on clinical, surgical and pathological features in women with endometrial cancer.

The impact of body mass index on radiotherapy technique in patients with early-stage endometrial cancer: a single-center dosimetric study.

Objective We aimed to evaluate the impact of body mass index on radiotherapy (RT) technique in patients with early-stage endometrial cancer. Materials and Methods Twenty-seven consecutive patients were included in the study and divided into 3 groups with respect to their body mass index (normal weight, 18.5–24.9 kg/m2; overweight, 25–29.9 kg/m2; obese, 30–39.9 kg/m2). Treatment plans using field-in-field (FIF) and 3-dimesional conformal RT (3D-CRT) were compared for the doses in the planning target volume (PTV), organs-at-risk (OAR) volumes, dose homogeneity index, and monitor unit counts required for the treatment. Results The FIF technique was superior to 3D-CRT with respect to the maximum and mean doses received by OAR and dose homogeneity index values. The subgroup analyses revealed that the maximum dose received by the right femur and the mean doses received by the rectum and bladder were significantly reduced only in obese patients (Ps = 0.021, 0.008, and 0.008, respectively). The FIF technique significantly reduced the PTV volumes irradiated with greater than 105% of the prescribed dose (P < 0.001). The volumes of bowel and bone marrow receiving more than the prescribed dose of 30 Gy were significantly reduced only in obese patients (Ps = 0.025 and 0.043, respectively). The volumes of bladder, bowel, and bone marrow receiving more than the prescribed dose of 45 Gy were significantly reduced in only obese patients (Ps = 0.011, 0.011, and 0.008, respectively). Conclusions Considering the lower maximum doses in OAR and PTV, we demonstrate the FIF technique to be more advantageous than 3D-CRT during adjuvant RT for early-stage endometrial cancer patients. This advantage is more prominent in obese patients. Therefore, FIF technique represents an effective pelvic RT treatment option for obese patients in clinics that do not have access to or prefer an alternative to intensity-modulated RT.

Aggressive rhabdoid meningioma with osseous, papillary and chordoma‐like appearance

Meningiomas are the most common primary intracranial tumors. They are usually benign and slowly growing; however, they may show histologically malignant features categorizing them into grade II or III of World Health Organization (WHO) classification. Rhabdoid meningioma (RM) is an uncommon meningioma variant categorized as WHO grade III. The clinical course of RM is determined by local recurrences, invasion of adjacent brain and/or dura, widespread leptomeningeal dissemination, remote metastases and fatal clinical outcome. Herein we report a case with recurrent aggressive left occipital parasagittal region RM in which the patient initially declined radiation treatment. The tumor was resected four times in 5 years. Histopathological examination revealed a rhabdoid meningioma with metaplastic, papillary and chordoid differentiation. Six months after her fourth operation the patient died of progressive disease. RM is a rare subtype of malignant meningioma and the role of different adjuvant therapeutic options are still unknown. Clinical presentation, radiological features and pathologic findings of this uncommon tumor are discussed.

Does spironolactone ameliorate trastuzumab-induced cardiac toxicity?

The ErbB2 receptor is a proto-oncogene associated with a poor prognosis in breast cancer. Trastuzumab, a humanized anti-ErbB2 antibody currently in clinical use, has proven to be an essential tool in the immunotherapy of breast carcinoma. Additionally, ErbB2 is involved in the growth and survival pathway of adult cardiomyocytes which accounts for the trastuzumab-induced cardiotoxicity. Moreover, in metastatic breast cancer patients treated with trastuzumab, endomyocardial biopsy documented focal vacuolar changes, pleomorphic mitochondria, myocardial cell hypertrophy, and mild interstitial fibrosis on electron microscopy without accompanying light microscopic abnormalities, a finding consistent with a reversible pattern of cardiac injury. On the other hand, aldosterone and mineralocorticoid receptor (MR) researches have experienced a revival after the discovery that aldosterone and MR are not only involved in the electrolyte and volume balance but also in the pathophysiological processes of the reno-cardiovascular system. Aldosterone has both genomic and nongenotropic effects on epidermal growth factor receptor (EGFR) expression. Genomic effect induces genomic up-regulation of the EGFR protein expression via EGFR promoter, whereas nongenotropic effect leads to the EGFR transactivation resulting in persistent pathophysiological effects including formation of extracellular matrix and myocardial hypertrophy. Spironolactone, an aldosterone receptor antagonist, is known to ameliorate the cardiac damage. The underlying mechanism for the genomic interactions seem to be the stimulation of the EGFR promoter by aldosterone-bound MR, which then dose-dependently enhances the EGFR protein levels, which may be successively inhibited by spironolactone. By the light of these findings, we hypothesize that spironolactone may ameliorate trastuzumab-induced cardiotoxicity via inhibition of transactivation of the EGFR by aldosterone and reversing myocardial hypertrophy. This issue warrants further studies.

Amelioration of radiation-induced lung injury by halofuginone: An experimental study in Wistar–Albino rats:

To evaluate effects of halofuginone (H) on radiation-induced lung injury (RILI), 60 rats were divided into six groups: Group (G) 1 control, G2 radiotherapy (RT) only, G3 and G4 2. 5 and 5 μg H and G5 and G6 RT + 2.5 and 5 μg H groups, respectively. A single dose of 12 Gy RT was given to both lungs. H was applied intraperitoneally with daily doses, until animals were killed at 6 and 16 weeks after RT. At 6th and 16th weeks of RT, five rats from each group were killed. Lung tissues were dissected for light and electron microscopy. Chronic inflammation, fibrosis and transforming growth factor-beta (TGF)-β scores of all study groups were significantly different at 6th and 16th week (p < 0.001). Chronic inflammation, fibrosis and TGF-β scores of G2 were higher than G5 and G6 at 6th and 16th weeks of RT. At 16th week, fibrosis and TGF-β scores of G5 were higher than G6 (p = 0.040 and 0.028, respectively). Electron microscopical findings also supported these results. Therefore, H may ameliorate RILI. The effect of the H was more prominent at higher dose and after long-term follow-up. These findings should be clarified with further studies.

The use of concurrent hormonotherapy and radiotherapy does not deteriorate radiation-induced cardiac toxicity:

Postmenopausal patients with breast cancer have two options for adjuvant endocrine therapy, tamoxifen and aromatase inhibitors (AIs) as well as radiotherapy (RT) and chemotherapy. However, there is limited data regarding the optimal sequencing of RT and tamoxifen/AIs. Thus, we aimed to evaluate the effects of tamoxifen and AIs on radiation-induced cardiotoxicity. Eighty ovariectomized rats were divided into eight groups (G). G1 was defined as a control group; G2, G3, G4, and G5 were RT, tamoxifen, anastrozle, and letrozole groups, respectively; G6, G7, and G8 were RT plus tamoxifen, anastrozle, and letrozole groups, respectively. Drugs were started 1 week before RT and continued until the animals were killed 16 weeks after RT. The heart tissues were then dissected and examined with light microscopy to determine endocardial thickness and cardiac fibrosis. The endocardial thickness scores of both RT alone and the tamoxifen groups as well as the cardiac fibrosis score of RT alone were higher than that the control group (p < 0.05 for all). There was no difference in the endocardial thickness and cardiac fibrosis scores of the RT-only group and the RT plus hormonotherapy groups (p > 0.05 for all). Concurrent administration of RT and hormonal therapy with either tamoxifen or AIs did not further amplify radiation-induced cardiac toxicity. This issue warrants further study.

Evaluation of the effect of changes in dose rate on rat lung cells.

The aim of this study is to evaluate the effect of dose rate (DR) on lung tissue. The rats included in the study were randomly grouped into 3 groups: Group (G) 1 was defined as control group, and in this group rats were sham irradiated. G2 was the group receiving a single dose of 12 Gy in DR of 300 monitor unit (MU)/min. G3 was the group receiving a single dose of 12 Gy in DR of 600 MU/min. Radiotherapy (RT) was applied under general anesthesia with 6-MV photon beams to both lungs. At the 6th and 16th week of the RT, animals from each group were killed for light and electron microscopy evaluation. We evaluated the scores of each group in the 6th and the 16th week and found that in G2, there were significant increases in the perivascular fibrosis (P = .018), interstitial fibrosis (P = .002), total inflammation (P = .040), and total fibrosis (P = .003) scores. In G3, we found statistically significant increases in perivascular fibrosis (P = .001), interstitial fibrosis (P = .002), and total fibrosis scores (P = .029). There was no significant difference in the total inflammation score in G3 (P = .225). When we compare G2 and G3 in the 6th week, we found significant increase in the interstitial thickening (P = .039) and total inflammation (P = .035) scores in G3. Dose rate per fraction may have an impact on normal tissue toxicity. The prominent effect of increased DR in lung tissue is fibrosis which should be kept in mind, especially in cases where higher doses per fraction are used.

Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging of a Patient with Squamous Cell Carcinoma of Prostate

Primary squamous cell carcinoma is an uncommon tumor of the prostate gland. We report a 77-year-old male patient with urinary frequency and constipation. Fine needle biopsy from prostate was suspicious of squamous cell carcinoma of the prostate. Whole body positron emission tomography/computed tomography scan revealed high fluorodeoxyglucose uptake in prostate gland. Transurethral resection confirmed the diagnosis. In contrast to prostatic adenocarcinoma, high fluorodeoxyglucose accumulation was observed in the primary tumor of the prostate gland.

HER-2 Mutations in Non-Small Cell Lung Cancer

Lung cancer is a heterogeneous and complex disease. Oncogenic driver mutations are critical for lung cancer development and serve as therapeutic targets. Oncogenic driver mutations are well defined in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and reactive oxygen species-1 (ROS-1) mutations. Human epidermal growth factor receptor-2 (HER-2) positivity and anti-HER-2 treatments are well studied in breast cancer. In non-small cell lung cancer (NSCLC), these treatment approaches are under investigation. In NSCLC, mutations of HER-2 are found in 2%–4% of cases. The most commonly encountered mutations are frame insertions in exon 20. There is no evident association between HER-2 amplification and HER-2 mutations. HER-2-targeted therapy needs further clinical investigations in NSCLC.