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.

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.

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.

Nasopharyngeal carcinoma radiotherapy with hybrid technique.

The aim of the study was to investigate the effect of the Hybrid technique which was created by combining of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of nasopharyngeal cancer (NPC) patients. 7 to 9 field IMRT, triple arc VMAT, and Hybrid plans were generated for 10 advanced stage NPC patients. The homogeneity index (HI) and the conformity index (CI) of planning target volumes (PTVs) were calculated for each technique to evaluate the plan quality. The techniques were compared in terms of plan quality, sparing of organs at risk (OARs), monitor units (MUs), and delivery time. Hybrid technique significantly improved the target dose homogeneity and the conformity for PTV70 and PTV60 compared to IMRT and VMAT. Hybrid plans significantly reduced the maximum dose of the brainstem sparing compared to the VMAT plans and also improved the sparing of spinal cord compared to IMRT and VMAT. The MUs and the delivery time of Hybrid plans were found to be between values for IMRT and VMAT plans. Hybrid technique can be useful when IMRT and VMAT techniques are not adequate alone in the treatment of NPC patients.

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.

Diagnostic value of serum M30 and M65 in patients with nasopharyngeal carcinoma.

M30 and M65 are circulating fragments of cytokeratin 18 released during apoptotic cell death and regarded as markers of cell death in patients with various tumor types. Our aim was to investigate the clinical and prognostic significance of the serum M30 and M65 concentrations in patients with advanced nasopharyngeal carcinoma. Thirty-two patients with nasopharyngeal cancer and 32 control subjects were investigated. Serum samples were obtained on first admission before any treatment was initiated. Serum M30 and M65 concentrations were measured by quantitative enzyme-linked immunosorbent assay. Median serum M30 (181.5 vs. 45.5 U/L, p < 0.001) and M65 (384.2 vs. 179.1 U/L, p < 0.001) concentrations were significantly higher in patients with advanced nasopharyngeal carcinomas than in controls. receiver operating characteristic (ROC) analysis showed that a cutoff for M30 of 225 U/L had a sensitivity of 62.5% and a specificity of 73.9% (area under the curve (AUC) = 0.592, 95% confidence interval (CI) 35.3-83.2, p = 0.44), while a cutoff for M65 of 423.4 U/L had a sensitivity of 75.1% and a specificity of 65.6% (AUC = 0.562, 95 % CI 36.0-76.5, p = 0.60). However, serum M30 and M65 were not important prognostic factors for progression-free survival. There were no statistically significant correlations between serum M30 and M65 concentrations and clinicodemographical variables. Serum M30 and M65 concentrations were found to have a diagnostic value in nasopharyngeal cancer. However, neither M30 nor M65 serum levels played a prognostic role in the outcome in nasopharyngeal cancer patients.

Practice patterns for oropharyngeal cancer in radiation oncology centers of Turkey.

AIMS AND BACKGROUND: The aim of the study was to review the current clinical practices of radiation oncologists involved in the treatment of oropharyngeal cancer. METHODS AND STUDY DESIGN: The daily practices of radiation oncology centers for patients diagnosed with oropharyngeal cancer in 2010 were evaluated by a two-part questionnaire that separately assessed the information of the participating center and the charts of the treated patients. RESULTS: A total of 22 centers participated in the study, and 105 oropharyngeal cancer patients reported for our review. The use of positron emission tomography was a common practice in staging and radiotherapy planning. Multidisciplinary head and neck cancer clinics were available in 14 (64%) centers and were absent in 8 centers. Thirty-six of the 105 patients were not evaluated by a multidisciplinary clinic before the initiation of therapy, and adjuvant radiotherapy administration was found to be higher in this group. Percutaneous endoscopic gastrostomy tube placement was not a routine practice in any of the centers. Seventy-five patients received chemotherapy - 46 concurrently with radiotherapy and 29 as induction chemotherapy. Two centers administered conventional radiotherapy alone, 20 centers conformal radiotherapy, and 7 centers were able to provide intensity-modulated radiotherapy. CONCLUSIONS: Across all the centers there were small differences in the pretreatment evaluation of patients with oropharyngeal cancer. The greatest difference was in the technical delivery of radiation, with most of the centers using conformal radiotherapy despite the increasing availability of intensity-modulated radiotherapy. The use of chemotherapy has more readily adopted the current international standards in the treatment of oropharyngeal cancer.

Olfactory bulb volume and olfactory function after radiotherapy in patients with nasopharyngeal cancer.

OBJECTIVE: Radiotherapy is the primary method of treatment for nasopharyngeal cancer (NPC) and many side effects were reported in patients receiving radiation to this area. This study was conducted to evaluate the long-term effects of radiotherapy following NPC on olfactory bulb (OB) volume and olfactory function. METHODS: Twenty-four patients with NPC who received radiotherapy at least 12 months ago were recruited. Fourteen healthy subjects with similar demographical characteristics were recruited as the healthy control group. All volunteers were subjected to a nasoendoscopical examination, and abnormalities that could potentially cause olfactory dysfunction were the exclusion criteria from the study. An experienced radiologist segmented the MRI coronal, axial and sagittal slices manually for three-dimensional OB volume measurement in a blinded manner. Olfactory function was assessed using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, and average score (0: worst, 7: best) was calculated as the total CCCRC olfactory score. RESULTS: The mean CCCRC score was 5.5 ± 1.1 for the nasopharyngeal cancer patients, whereas the mean score of healthy control group was 6.4 ± 0.4. There was a significant difference in the olfactory scores (p=0.003). The mean OB volume in the NPC group was 46.7 ± 12.1mm(3). Among the patients with NPC, the cisplatin receiving group had a mean OB volume of 47.2mm(3), whereas the cisplatin+docetaxel receiving group had a mean OB volume of 46.5mm(3), and they were similar. The MRI measurement of the healthy control group was 58.6 ± 13.8mm(3). The OB volumes of the healthy control group were significantly higher (p<0.05). CONCLUSION: Radiotherapy following nasopharyngeal cancer results in a diminished OB volume and deteriorated olfactory function. Chemosensory olfactory dysfunction might be a contributing factor to lack of appetite, cancer cachexia and consequent lowered quality of life in NPC patients.

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.

The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the head and neck region: review of 30 cases.

BACKGROUND: Thirty adult patients with head and neck soft tissue sarcoma (HNSTS) treated between 1987 and 2000 were retrospectively analysed. PATIENTS AND METHODS: The most frequent histopathological subtypes were chondrosarcomas (27%) and malignant fibrous histiocytoma (20%). The surgical resection was performed in 25 of the 30 patients (83%). Twenty-three patients in the surgical resection arm received postoperative radiotherapy. RESULTS: Five-year local control rates for patients with negative surgical margins (n=9), microscopically positive disease (n=10), gross residual disease (n=6) and inoperable cases (n=5) were 64, 70, 20 and 0%, respectively. However, there was no significant difference in local control between patients with negative or microscopically positive disease who received postoperative radiotherapy (71 vs. 70%). The patients who received doses>or=60 Gy had significantly higher local control rates than the ones who received doses lower than 60 Gy (p=0.048). The local control rates were lower in patients with grade 2-3 tumours when compared with grade 1 tumours (44 vs. 83%). The median overall survival of whole group was 31 months. Median survivals of patients receiving both surgery and radiotherapy with negative and microscopically positive margins were significantly better than patients who were not treated with surgery (34.8 and 36 vs. 13.3 months). CONCLUSION: Our results confirm that the optimal treatment of HNSTSs is complete surgical excision, and that postoperative adjuvant radiotherapy clearly improves local control.

Assessment of quality of life of nasopharyngeal carcinoma patients with EORTC QLQ-C30 and H&N-35 modules.

PURPOSE: The current study reports on long-term quality of life (QoL) status after conventional radiotherapy in 187 nasopharyngeal carcinoma patients from 14 centers in Turkey. PATIENTS AND METHODS: Patients with the diagnosis of nasopharyngeal carcinoma, who were treated in 14 centers in Turkey with minimum 6 months of follow-up and were in complete remission, were asked to complete Turkish versions of EORTC QLQ-C30 questionnaire and the HN-35 module. Each center participated with the required clinical data that included age at diagnosis, gender, symptoms on admission, follow-up period, treatment modalities, radiotherapy dose, and AJCC 1997 tumor stage. Each patient's 33 QoL scores, which included function, global health status, and symptoms, were calculated as instructed in EORTC QLQ-C30 scoring manual. All of the scales and single-item measures range from 0 to 100. A high score represents a higher response level. Kruskal-Wallis and Mann-Whitney U nonparametric tests were used for comparisons. RESULTS: One hundred eighty-seven patients with median age of 46 years (range, 16-79 years) participated and completed the questionnaires. Median follow-up time was 3.4 years (range, 6 months-24 years). All patients have received external-beam radiotherapy. Beside external-beam radiotherapy, 59 patients underwent brachytherapy boost, 70 patients received concomitant chemotherapy, and 95 patients received adjuvant/neoadjuvant chemotherapy. Most of the patients in the analysis (75%) were in advanced stage (Stage III, n = 85 [45.4%]; Stage IV, n = 55 [29%]). Mean global health status was calculated as 73. Parameters that increased global health status were male gender, early-stage disease, and less than 4-year follow-up (p < 0.05). Functional parameters were better in males and in early-stage disease. Factors that yielded better symptom scores were short interval after treatment (10 scores), male gender (7 scores), and lower radiation dose (6 scores). Neoadjuvant or adjuvant chemotherapy did not have any effect on QoL, whereas concomitant chemotherapy adversely affected 5 symptom scores. CONCLUSION: Quality of life is adversely affected in our nasopharyngeal carcinoma patients treated with combined therapies. The factors that adversely affect quality of life are advanced tumor stage, female gender, and long-term follow-up. Further controlled studies to evaluate both preradiotherapy and postradiotherapy status are necessary to clarify the contribution of each treatment modality to QoL.

P53 overexpression in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a characteristic tumor displaying epidemiological, genetic and regional distribution properties and is unique by its natural behavior and therapy. Investigation of the molecular and biological changes, gene amplifications and activations that occur during carcinogenesis and progression can provide new insight into the pathology of the disease and may add biological factors that can be used as new prognostic markers. The p53 tumor suppressor gene is the most frequently mutated gene in human cancer. Although point mutations in the p53 gene are observed in nasopharyngeal cancer, the mutation rate is lower than in other tumors. Immunohistochemical studies have shown significant p53 overexpression in NPC material. In this study, p53 protein immunoreactivity was investigated in paraffin sections of primary nasopharyngeal tumors and metastatic cervical lymph nodes and association with clinical and histopathological characteristics was evaluated. Ninety-seven paraffin sections from 81 patients with NPC treated from 1990 to 1996 were examined by immunohistochemistry and were correlated with clinical features and treatment outcome. Among a total of 97 samples, positive staining for p53 protein was observed in 83 (85.5%) samples while no staining was found in 14 (14.5%) cases. Immunoreactivity was observed in 62 (81.5%) of the primary nasopharyngeal biopsy specimens. The correlation between p53 expression and histological type, stage, age and sex distributions was tested. After statistical analysis according to Chi-square test and Yates' correction, no significant difference was demonstrated (p>0.05). There was no statistically significant correlation with p53 immunoreactivity and overall and disease-free survival. Although the association between NPC and p53 is not clear, our study confirms that p53 overexpression is present in a considerable subset of patients with NPC.

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.