Nasopharyngeal carcinoma in children: Multimodal treatment and long-term outcome of 92 patients in a single center over a 28-year period.

OBJECTIVES: The aim of the study was to evaluate the long-term outcome and late effects in pediatric patients with nasopharyngeal carcinoma (NPC) treated with neoadjuvant chemotherapy (NACT), followed by radiotherapy (RT). METHODS: Ninety-two children (65 male, 27 female) diagnosed with NPC between 1989 and 2017 in the Istanbul University, Institute of Oncology were evaluated retrospectively. NACT consisted of three cycles of cisplatin-containing regimen every 3 weeks, followed by RT. RESULTS: The median age was 13 years (5-18 years). Most had locoregionally advanced disease (stage III/IVA/IVB) and five had distant metastases at presentation. At a median follow-up of 108 months (3-332 months), 5- and 10-year overall survival rates and event-free survival rates were 87.5%, 79.7% and 82.1%, 78.9%, respectively. Three patients with distant metastasis are long-term survivors. Thirteen patients relapsed at a median of 8 months (2-23 months). Hypothyroidism (36%) and xerostomia (25%) were the most frequent long-term treatment-related toxicities. Nine second malignancies developed in eight patients, eight in the irradiated field at a median of 14 years (range 5-26 years), five of whom are long-term survivors after curative surgery. CONCLUSIONS: Three courses of cisplatin-containing NACT, followed by RT lead to high survival and locoregional control rate in advanced stage NPC in children. Patients with distant metastasis should also be treated with curative intent by systemic chemotherapy and locoregional radiotherapy. Patients should be followed closely for recurrences and long-term morbidities including second malignancies, which may be treated with curative surgeries if diagnosed early.

Do circulating long non-coding RNAs (lncRNAs) (LincRNA-p21, GAS 5, HOTAIR) predict the treatment response in patients with head and neck cancer treated with chemoradiotherapy?

Long non-coding RNAs (lncRNAs) have been shown to be aberrantly expressed in head and neck cancer (HNC). The aim of the present study was to evaluate plasma levels of three lncRNA molecules (lincRNA-p21, GAS5, and HOTAIR) in the treatment response in HNC patients treated with radical chemoradiotherapy (CRT). Forty-one patients with HNC were enrolled in the study. Most of the patients had nasopharyngeal carcinoma (n = 27, 65.9 %) and locally advanced disease. Blood was drawn at baseline and treatment evaluation 4.5 months after therapy. lncRNAs in plasma were measured by semiquantitative PCR. Treatment response was evaluated according to clinical examination, RECIST and PERCIST criteria based on magnetic resonance imaging (MRI), and positron emission tomography with computed tomography (PET/CT) findings. Complete response (CR) rates were 73.2, 36.6, and 50 % for clinical investigation, PET/CT-, or MRI-based response evaluation, respectively. Predictive value of lncRNAs was investigated in patients with CR vs. those with partial response (PR)/progressive disease (PD). We found that post-treatment GAS5 levels in patients with PR/PD were significantly higher compared with patients with CR based on clinical investigation (p = 0.01). Receiver operator characteristic (ROC) analysis showed that at a cutoff value of 0.3 of GAS5, sensitivity and specificity for clinical tumor response were 82 and 77 %, respectively. Interestingly, pretreatment GAS5 levels were significantly increased in patients with PR/PD compared to those with CR upon MRI-based response evaluation (p = 0.042). In contrast to GAS5, pretreatment or post-treatment lincRNA-p21 and HOTAIR levels were not informative for treatment response. Our results suggest that circulating GAS5 could be a biomarker in predicting treatment response in HNC patients.

Cisplatin-docetaxel induction chemotherapy for patients with nasopharyngeal carcinoma in a non-endemic cohort.

This is the report on our clinic's 15 years of experience (2004-2018) on nasopharyngeal carcinoma (NPC), treated with induction chemotherapy (IC) and subsequent concomitant chemoradiotherapy (CCRT), comprising population characteristics and treatment outcomes of 203 patients with non-metastatic NPC. IC comprised docetaxel (75 mg/m2) and cisplatin (75 mg/m2) combination (TP). Concurrent cisplatin (P) was applied either weekly (40 mg/m2, 32 cases) or every-3-week (100 mg/m2, 171 cases). The median follow-up duration was 85 months (range, 5-204 months). Overall and distant failure rates were observed in 27.1% (n = 55) and 13.8% (n = 28) patients, respectively. The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 84.1%, 86.4%, 75%, and 78.7% respectively. The overall stage was an independent prognostic factor for the LRRFS, DMFS, DFS, and OS. The WHO histological type was a prognostic factor for the LRRFS, DFS, and OS. Age was a prognostic factor for the DMFS, DFS, and OS. Concurrent P schedule was independent prognostic only the LRRFS.

Multiple atypical recurrent meningiomas 13 years after radiotherapy for unilateral retinoblastoma: case report and review of the literature.

Radiotherapy is an important treatment modality for intracranial malignancies. Improved survival rates were achieved via a combination of surgery, chemotherapy and radiotherapy. On the other hand, improved survival rates made long-term complications of radiotherapy more apparent. Secondary neoplasms due to cranial irradiation are encountered more commonly in neurosurgical practice. Radiation-induced meningiomas are recognized as a common late complication of radiotherapy. However, radiation-induced meningiomas after radiotherapy for retinoblastoma have been reported rarely. Herein we report a patient who harboured multiple meningiomas 13 years after radiotherapy for unilateral retinoblastoma, which were recurrent despite surgical removal and chemotherapy.

Promising Outcomes in Acromegaly Patients Receiving CyberKnife Stereotactic Hypofractionated Radiotherapy.

BACKGROUND: The primary treatment for patients with acromegaly has traditionally been transsphenoidal surgery, with decreasing reliance on radiotherapy (RT) due to advancements in pharmacotherapy (PT). Despite these advancements, a substantial portion of patients still face persistent acromegaly, necessitating novel treatment approaches. This study investigates the role of CyberKnife Stereotactic Hypofractionated Radiotherapy (CK-HFRT) in persistent acromegaly. OBJECTIVE: The primary objective was to assess the impact of CK-HFRT on endocrine remission (ER) rates while maintaining acceptable toxicity levels. METHODS: The study retrospectively analyzed 31 consecutive patients with acromegaly who received CK-HFRT following multiple unsuccessful surgeries and prolonged PT without ER. Various CK-HFRT dose fractionation regimes were administered, and dose volume histograms were evaluated. Tumor control, cured disease (CD), endocrine remission (ER) rates, and overall survival were estimated at a median follow-up of 62 months. Acute and late toxicity, including pituitary insufficiency and radiation-induced optic neuropathy (RION), were also assessed. RESULTS: At 62 months of follow-up, the study group demonstrated excellent tumor control with 100% nonprogressive adenomas. Endocrine remission was achieved in 86.7% of patients, with a 22.4% CD rate at five years. Pituitary insufficiency occurred in 32.3% of patients, and no cases of RION were reported. The study observed three deaths related to cardiovascular diseases, all in patients receiving PT. Overall survival at five years was 79.2%. CONCLUSION: CyberKnife stereotactic hypofractionated radiotherapy, as an adjunct to PT, provides a viable treatment option for patients with persistent acromegaly following unsuccessful surgeries. The therapy results in substantial ER rates and tumor control while minimizing the risk of permanent radiation-induced optic neuropathy. However, the decision to administer CK-HFRT should be individualized, considering the patient's overall condition and treatment history.

Efficacy and Safety of Stereotactic Radiotherapy in Cushing's Disease: A Single Center Experience.

OBJECTIVE: To determine the efficacy and safety of stereotactic radiotherapy (RT) in patients with Cushing's disease (CD). METHODS: The study included 38 patients [31 patients who received gamma knife radiosurgery (GKS) and 7 patients who received cyberknife hypofractionated RT (HFRT)] with CD. Hormonal remission was considered if the patient had suppressed cortisol levels after low dose dexamethasone, normal 24-hour urinary free cortisol (UFC), and lack or regression of clinical features. RESULTS: Biochemical control after RT was observed in 52.6% of the patients with CD and median time to hormonal remission was 15 months. Tumor size control was obtained in all of the patients. There was no significant relationship between remission rate and laboratory, radiological and pathological variables except for preoperative UFC. Remission rate was higher in patients with lower preoperative UFC. Time to remission increased in parallel to postoperative cortisol and 1mg DST level. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to hormonal remission. CONCLUSION: In this current single center experience, postoperative cortisol and 1mg DST levels were found as the determinants of time to remission. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to biochemical control . This latter finding might suggest a radioprotective effect of cortisol lowering medication use on peri-RT period.

Effectiveness of Black Mulberry Molasses in Prevention of Radiotherapy-Induced Oral Mucositis: A Randomized Controlled Study in Head and Neck Cancer Patients.

OBJECTIVES: Radiation-induced oral mucositis is one of the problems experienced by 70%-80% of patients receiving radiation therapy (RT). This randomized controlled trial assessed the effectiveness of black mulberry molasses in the prevention of oral mucositis in head and neck cancer patients receiving RT. INTERVENTIONS AND OUTCOME MEASURES: Eighty head and neck cancer patients scheduled to undergo RT to the oropharyngeal mucosa were randomly assigned to receive RT (42) or RT plus mulberry molasses (38). The research data were collected with a Patient Description Form, Common Terminology Criteria for Adverse Events, version 4.0, an Oral Assessment Guide, and the University of Washington Quality of Life Assessment Questionnaire. RESULTS: The incidence and severity of oral mucositis were lower in the black mulberry molasses group. However, black mulberry molasses usage was an only independent and significant factor in prevention of mucositis [HR 0.63 (%95 GI 0.40-0.98)]. There were no differences between the quality of life scores of experimental and control groups. CONCLUSIONS: This randomized controlled study showed that black mulberry molasses usage is an effective intervention in the prevention of the radiation-induced mucositis of head and neck cancer patients. However, to confirm these results, further studies are needed.

Prognostic significance of hemoglobin concentration in nasopharyngeal carcinoma: does treatment-induced anemia have negative effect?

PURPOSE: To assess the value of hemoglobin concentration (HC) in predicting treatment outcomes in nasopharyngeal carcinoma (NPC) patients treated with chemotherapy (CT) and radiotherapy (RT). PATIENTS AND METHODS: Ninety-eight NPC patients treated with three courses of platinum-based neoadjuvant CT (NCT) and conventional RT were grouped as having normal HC (> or = 12.0 g/dl in females and > or = 13 g/dl in males), having mild anemia (MA) (13.0 g/dl > Hb > or = 11 g/dl in males, 12.0 g/dl > Hb > or = 11 g/dl in females) and having severe anemia (SA) (Hb < 11 g/dl). Massive decrease in HC (MDHC) was defined as > or = 1.5 g/dl decline with NCT. Along with other known risk factors (sex, age, histopathology, T stage, N stage, bilateral neck involvement, cranial nerve involvement and total RT time), the prognostic value of SA and MDHC were evaluated by Cox-regression. RESULTS: SA increased from 7 to 33% with NCT (p < 0.0001). Patients with SA had lower 5-year locoregional control (LRC) (49 vs. 73%, p = 0.03), disease-free survival (DFS) (42 vs. 68%, p = 0.01) and overall survival (OS) (43 vs. 69%, p = 0.01) rates than patients with normal HC or MA. The presence of MDHC worsened 5-year LRC (p = 0.002), DFS (p = 0.001) and OS (p = 0.02) rates. In multivariate analyses, MDHC and SA had pronounced effect on LRC and survival, respectively. CONCLUSION: MDHC and SA adversely affect treatment outcome in NPC patients treated with CT and RT. This may favour concomitant scheduling of RT and CT over neoadjuvant setting. Correction of HC before RT can improve the efficacy of RT and should be further evaluated.

Carcinoma of the tongue: a case-control study on etiologic factors and dental trauma.

BACKGROUND: Carcinoma of the tongue is the most common intra-oral malignancy in Western countries. Incidence and mortality rates have increased in recent years, and survival has not improved. This study aimed to determine etiologic factors for tongue cancer with age-sex matched case-control data. MATERIALS AND METHODS: 47 patients with carcinoma of the tongue referred to our oral medicine clinic between years 2005-2006 were analyzed and compared with control group data. The medical records , including family history of cancer, dental trauma, and history of abuse of alcohol and tobacco products was recorded for all subjects. Chi square comparison tests and linear regression analysis were performed using the SPSS program for statistics. RESULTS: Patient and randomly selected control groups each consisted of 30 male and 17 female subjects with mean ages 53.2 (± 12.6) and 52.6 (± 11.5) years respectively. Smoking and alcohol abuse proportions were significantly higher in the patient group (p=0.0001, p<0.0001 respectively). Chronic mechanical trauma was observed in 44.7% of the patients and 17.0% of the control group (p=0.004). Similarly, family history of cancer of any type (for the first degree relatives) was found to be more common in the patient group (p=0.009). On regression analysis, alcohol abuse, family history of cancer, smoking, chronic mechanical traumas appeared as significant etiologic factors (p=0.0001). CONCLUSIONS: We believe that field cancerization may become evident in oral and oropharyngeal mucosa with multiple steps of molecular changes starting from the first sign of dysplasia with chronic exposure to etiological factors. Chronic trauma cases need particular attention to search for very early signs of cancer.

Induction chemotherapy with docetaxel and cisplatin is highly effective for locally advanced nasopharyngeal carcinoma.

Radiotherapy (RT) with concomitant chemotherapy (CT) has improved the therapeutic outcome of patients with locally advanced nasopharyngeal carcinoma (LANC). However, the importance of induction CT before definitive therapy is still undefined. Patients (n=59) who had LANC were included in this retrospective study. They received induction CT consisting of cisplatin and docetaxel followed by definitive RT with cisplatin. The median age was 49 years (18-68). All patients were of stages II (15%), III (63%) and IV (22%). Fifty eight patients could receive 3 cycles of CT. Except one patient, there was no grade 3 or 4 toxicity during induction CT. Chemoradiotherapy could be given to 49 patients (83%). Twelve percent of patients had complete response after induction CT and this number had increased to 95% after the completion of the therapy. Objective responses (complete and partial) were 100% after the completion of the therapy. Median follow up time was 29 months. Nine patients had relapse (2 had local only, 4 distant, 3 local and distant). Three patients who had both local and distant relapse died during follow-up. Three year overall and progression free survival rates were 94.9% and 84.7%, respectively. Induction CT with docetaxel and cisplatin is a feasible and tolerable treatment for patients with LANC.

Effects of amifostine on healing of microvascular anastomoses, flap survival, and nerve regeneration with preoperative or postoperative irradiation.

Amifostine is an organic thiophosphate compound, which has both cytoprotective and radioprotective effects. An experimental study was undertaken to investigate the effects of its use on reconstructive surgery in cancer treatment. One hundred and twenty guinea pigs were divided into three equal groups to investigate flap survival and healing, patency of microvascular anastomoses, and nerve regeneration, respectively. The groups were subdivided in such a way that they were given either preoperative or postoperative radiotherapy, with or without amifostine treatment. Macroscopic and planimetric examination, light and electron microscopy, and histomorphometric analyses were performed to evaluate flap survival and healing, patency of arterial anastomoses, and nerve regeneration. Although flap survival rates were not affected, significantly better flap healing was observed in the postoperative radiotherapy subgroup with amifostine treatment. However, amifostine treatment did not result in a statistically significant difference in terms of anastomotic patency and nerve regeneration with either preoperative or postoperative radiotherapy.