Radiotherapy Results in Locally Advanced Sinonasal Cancer: Turkish Society for Radiation Oncology, Head and Neck Study Group 01-005.

OBJECTIVES: This study aims to examine the treatment outcomes and related factors in locally advanced sinonasal cancer across Turkiye. METHODS: Twelve centers participants of the Turkish Society for Radiation Oncology Head and Neck Study Group attended the study. One hundred and ninety-four patients treated with intensity-modulated radiation therapy between 2001 and 2021 were analyzed retrospectively. The survival analysis was performed using the Kaplan-Meier method. Acute and late toxicity were recorded per Common Toxicity Criteria for Adverse Events V4.0. RESULTS: The median age was 58 years and 70% were male. The majority of tumors were located in maxillary sinus (59%). Most of the patients (%83) had T3 and T4A disease. Fifty-three percent of patients were in stage 4A. Radiotherapy was administered to 80% of the patients in the adjuvant settings. Median 66 Gy dose was administered in median 31 fractions. Chemotherapy was administered concomitantly with radiotherapy in 45% of the patients mostly with weekly cisplatin. No grade ≥4 acute and late toxicity was observed. The median follow-up was 43 months. The 5-year and 10-year overall survival (OS); locoregional recurrence-free survival (LRFS); distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 61% and 47%; 69% and 61%; 72%, and 69%, and 56% and 49%, respectively. In the multivariate analysis, several factors demonstrated significant influence on OS, such as performance status, surgery, and lymph node involvement. Moreover, surgery was the key prognostic factor for LRFS. For DMFS, lymph node involvement and surgical margin were found to be influential factors. In addition, performance status and lymph node involvement were identified as significantly affecting PFS. CONCLUSIONS: In our study, the authors obtained promising results with IMRT. Performance status, lymph node involvement, and surgery emerged as the primary factors significantly influencing OS.

ESTRO ACROP and SIOPE recommendations for myeloablative Total Body Irradiation in children.

BACKGROUND AND PURPOSE: Myeloablative Total Body Irradiation (TBI) is an important modality in conditioning for allogeneic hematopoietic stem cell transplantation (HSCT), especially in children with high-risk acute lymphoblastic leukemia (ALL). TBI practices are heterogeneous and institution-specific. Since TBI is associated with multiple late adverse effects, recommendations may help to standardize practices and improve the outcome versus toxicity ratio for children. MATERIAL AND METHODS: The European Society for Paediatric Oncology (SIOPE) Radiotherapy TBI Working Group together with ESTRO experts conducted a literature search and evaluation regarding myeloablative TBI techniques and toxicities in children. Findings were discussed in bimonthly virtual meetings and consensus recommendations were established. RESULTS: Myeloablative TBI in HSCT conditioning is mostly performed for high-risk ALL patients or patients with recurring hematologic malignancies. TBI is discouraged in children <3-4 years old because of increased toxicity risk. Publications regarding TBI are mostly retrospective studies with level III-IV evidence. Preferential TBI dose in children is 12-14.4 Gy in 1.6-2 Gy fractions b.i.d. Dose reduction should be considered for the lungs to <8 Gy, for the kidneys to ≤10 Gy, and for the lenses to <12 Gy, for dose rates ≥6 cGy/min. Highly conformal techniques i.e. TomoTherapy and VMAT TBI or Total Marrow (and/or Lymphoid) Irradiation as implemented in several centers, improve dose homogeneity and organ sparing, and should be evaluated in studies. CONCLUSIONS: These ESTRO ACROP SIOPE recommendations provide expert consensus for conventional and highly conformal myeloablative TBI in children, as well as a supporting literature overview of TBI techniques and toxicities.

Increased radiosensitivity and impaired DNA repair in patients with STAT3-LOF and ZNF341 deficiency, potentially contributing to malignant transformations.

STAT3 plays an important role in various complex and sometimes contradictory pathways such as proliferation, differentiation, migration, inflammation, and apoptosis. The transcriptional activity of the STAT3 gene is controlled by a transcription factor called ZNF341. There is insufficient data on radiation sensitivity and post-radiation DNA repair in STAT3- loss-of-function (LOF) patients. We aimed to investigate the radiosensitivity in patients with STAT3-LOF and ZNF341 deficiency. Twelve patients with STAT3-LOF and four ZNF341-deficiency patients were recruited from three clinical immunology centers in Turkey and evaluated for radiosensitivity by the Comet assay, comparing to 14 age- and sex-matched healthy controls. The tail length (TL) (µm), percentage of DNA in the tail (TDNA%), and olive tail moment (OTM) (arbitrary units) were evaluated at the same time for baseline (spontaneous), initial (immediately after 2 Gy irradiation), and recovery (2 h after irradiation) periods by using a computerized image-analysis system, estimating DNA damage. Except for a patient with ZNF341 deficiency who developed nasal cell primitive neuroendocrine tumor and papillary thyroid cancer during the follow-up, there was no cancer in both groups. During the recovery period of irradiation, TL, TDNA%, and OTM values of healthy controls decreased rapidly toward the baseline, while these values of patients with STAT3-LOF and ZNF341 deficiency continued to increase, implying impaired DNA repair mechanisms. Increased radiosensitivity and impaired DNA repair were demonstrated in patients diagnosed with STAT3-LOF and ZNF341 deficiency, potentially explaining the susceptibility to malignant transformation.

Why do some patients with stage 1A and 1B endometrial endometrioid carcinoma experience recurrence? A retrospective study in search of prognostic factors.

OBJECTIVES: Endometrial endometrioid carcinoma (EEC) is the most encountered subtype of endometrial cancer (EC). Our study aimed to investigate the factors affecting recurrence in patients with stage 1A and 1B EEC. MATERIAL AND METHODS: Our study included 284 patients diagnosed with the International Federation of Gynecology and Obstetrics stage 1A/1B EEC in our center from 2010 to 2018. The clinicopathological characteristics of the patients were obtained retrospectively from their electronic files. RESULTS: The median age of the patients was 60 years (range 31-89). The median follow-up time of the patients was 63.6 months (range 3.3-185.6). Twenty-two (7.74%) patients relapsed during follow-up. Among the relapsed patients, 59.1% were at stage 1A ECC, and 40.9% were at stage 1B. In our study, the one-, three-, and five-year recurrence-free survival (RFS) rates were 98.9%, 95.4%, and 92.9%, respectively. In the multivariate analysis, grade and tumor size were found to be independent parameters of RFS in all stage 1 EEC patients. Furthermore, the Ki-67 index was found to affect RFS in stage 1A EEC patients, and tumor grade affected RFS in stage 1B EEC patients. In the time-dependent receiver operating characteristic curve analysis, the statistically significant cut-off values were determined for tumor size and Ki-67 index in stage 1 EEC patients. CONCLUSIONS: Stage 1-EEC patients in the higher risk group in terms of tumor size, Ki-67, and grade should be closely monitored for recurrence. Defining the prognostic factors for recurrence in stage 1 EEC patients may lead to changes in follow-up algorithms.

Evaluation of late effects of postoperative radiotherapy in patients with medulloblastoma.

We aimed to evaluate long-term toxicity in children with medulloblastoma treated with postoperative radiotherapy (RT). This study included 21 patients aged 4-16 who had been diagnosed with medulloblastoma. All of the patients in the study received postoperative craniospinal RT. Postoperative RT followed by chemotherapy was the treatment protocol. A total of 13 patients (62%) received chemotherapy concurrently with RT. Overall survival was 50 months (range, 1-169 months) and disease-free survival was 39 months (range, 4-171 months). In the data analysis, the heights of 11 patients (91.6%) were found to be below 50% on the height curve, and 8 (66.6%) patients had weights below 50% on the weight curve. Mean sitting height was 72.58 ± 6.33 cm, and this was statistically correlated with parameters such as LH level (p=0.037), testosterone level (p=0.020), height (p=0.002), weight (p=0.033) and age at diagnosis (p=0.002). Radiation therapy for medulloblastoma seems to have a late toxic effect on long-term survivors. With the improving survival rate of medulloblastoma patients, RT doses should be as low as possible without sacrificing efficacy.

[Our results of postoperative radiation therapy in patients with salivary gland cancer]. / Tükürük bezi kanserli olgularda ameliyat sonrasi radyoterapi sonuçlarimiz.

OBJECTIVES: This study aims to evaluate our single center experience in patients with a salivary gland tumor receiving postoperative radiation therapy (RT). PATIENTS AND METHODS: Between January 1996 and December 2011, the records of 34 salivary gland tumor patients who were operated and referred to our clinic for adjuvant RT were retrospectively analyzed. Radiation therapy was applied to the primary tumor and lymphatics at a median dose of 60 Gy (54 to 60 Gy) with 1.8-2 Gy/fraction. RESULTS: The median follow-up was 38 months (range, 3 to 204 months). The most common site of involvement was the parotid gland in 21 patients (62%), followed by the submandibular gland in 11 patients (%24) and minor salivary gland in two patients (9%). Five-year overall survival (OS) was 49% (range, 3 to 206 months) and disease free survival (DFS) was 61% (range, 1 to 173 months). Six patients had local or regional recurrences (18%), while 13 patients (38%) had distant metastasis. A tumor size larger than 4 cm, over six weeks referral time to RT, and existence of metastatic lymph node were found to be poor prognostic factors for OS (p=0.023, p=0.039, respectively), and DFS (p=0.046). While extracapsular involvement significantly reduced the DFS and OS (p=0.022, p=0.050, respectively), overall RT time affected DFS alone (p=0.046). CONCLUSION: We recommend adjuvant RT in high-risk patients operated due to a salivary gland tumor.

The evaluation of bcl-2 expression as a prognostic marker in early stage laryngeal cancer.

AIMS AND BACKGROUND: To evaluate the effect of bcl-2 expression on the local control and overall survival of patients with early stage laryngeal cancer treated with radiotherapy alone. METHODS AND STUDY DESIGN: We included 53 patients with stage Tis, T1, and T2 laryngeal cancer who were irradiated in our department. Paraffin blocks of all biopsy specimens were subjected to immunohistochemical analysis with a bcl-2 oncoprotein mouse clone 124 Scytek kit. RESULTS: The mean follow-up time was 61 months (range, 7-166). Local-regional recurrence was observed in 10 (19%) patients. Forty-three patients (81%) had negative bcl-2 staining, 5 patients (9%) had + staining, 3 patients (6%) ++ staining, and 2 patients (4%) +++ staining. No relationship was detected between bcl-2 expression and local control or overall survival. The emergence of a recurrence and a younger age (<50 years) were significantly related to poor overall survival (P = 0.000 and P = 0.021, respectively). Patients with hemoglobin levels in the middle of radiotherapy and at the end of radiotherapy higher than 13 g/dl had improved overall survival in multivariate analyses (P = 0.002 and P = 0.001, respectively). Regarding local control, the following were poor prognostic factors: smoking more than 20 cigarettes a day (P = 0.001) and being younger than 50 years of age (P = 0.001). CONCLUSIONS: No correlation was observed between bcl-2 expression and local control or overall survival. Whereas hemoglobin level, age and existence of a recurrence had a prognostic impact on overall survival, patient age and smoking status influenced local control rates.