A Single-center Experience of Radiotherapy in Pediatric Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Chest Wall.

AIM: To evaluate the treatment results, prognostic parameters, and treatment-related toxicity in patients with Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) of the chest wall who underwent surgery, chemotherapy, and radiotherapy (RT) in a tertiary referral center. METHODS: The data of 24 patients under 18 years of age with a histologic diagnosis of ES/PNET in the chest wall that received RT in our department between February 2003 and July 2020 were retrospectively evaluated. RT was applied to the primary site±whole involved chest wall and to the whole lung in patients with lung metastasis. RESULTS: The median age was 8.5 years (range: 1.5 to 17 y), 15 (63%) patients were female and 9 were male (37%). The tumor localization was extrathoracic in 18 (75%) and intrathoracic in 6 (25%) patients. Mediastinal lymph node and distant metastasis (DM) was present in 5 (21%) and 4 (16%) cases at diagnosis, respectively. The median follow-up after RT was 47 months (range: 11 to 162 mo). The 2-year and 5-year overall survival, event-free survival, local recurrence-free survival, and pleural recurrence-free survival were 83% and 48%, 48% and 42%, 74% and 48%, and 61% and 52%, respectively. The overall local control rate was 83% and the pleural control rate was 67%. RT was well tolerated, with 1 case of grade 3 acute dermatitis and 1 case of grade 3 subacute radiation pneumonitis. Late toxicity was observed in 3 (13%) cases. CONCLUSION: Long-term survival can be achieved with extended-field RT even in patients with ES/PNET of the chest wall with DM. The low toxicity rates allow us to draw the conclusion that RT with modern techniques is an effective and safe treatment modality for these patients.

Stereotactic radiotherapy for head and neck paragangliomas: How long should we wait for treatment response?

BACKGROUND AND PURPOSE: Stereotactic radiotherapy (SRT) is an effective treatment for head & neck (H&N) paragangliomas. Nevertheless, the timeline for achieving a tumor-volume-reduction (TVR) remains unclear. MATERIALS AND METHODS: Sixty-three cases with H&N paragangliomas received definitive SRT and were evaluated retrospectively. Statistical Package for the Social Sciences (SPSS) v23.0 (IBM, Armonk, NY, USA) was used for statistics. RESULTS: Sixty-eight lesions were irradiated, with glomus jugulotympanicum being the most common location (44 %). Median tumor diameter and volume were 3 cm (range, 1-7.6 cm) and 15.4 cm3 (range,1-185 cm3), respectively. Median dose was 25 Gy (range, 12-37.5 Gy) in 5 fractions (range, 1-5 fractions). Median follow-up was 40 months (range, 3-184 months). Treatment response, evaluated at a median 4.6 months post-SRT (range: 3-11 months), revealed TVR in 26 cases (41 %). During follow-up, 13 additional cases showed TVR, resulting in an overall TVR rate of 62 %. The median duration for attaining TVR was 9 months (range, 3-36 months) after SRT, and TVR occurred ≥ 12 months in 42 % of cases. Patients without prior surgery (p = 0.03) and with a longer follow-up (p = 0.04) demonstrated a higher rate of TVR. The likelihood of TVR tends to increase as the SRT dose increases (p = 0.06). Overall local control (LC) rate was 100 %. No ≥ grade 3 acute or late toxicities were observed. CONCLUSION: While SRT demonstrates an excellent LC rate for H&N paragangliomas, it's important to note that the response to treatment may require time. TVR may last beyond the initial year of treatment in a substantial proportion of patients.

Role of hypofractionated stereotactic radiotherapy for primary optic nerve sheath meningioma.

Background: Optic nerve sheath meningiomas (ONSM) are rare tumors potentially causing visual deficits. This study aims to report the anatomic and visual outcomes of patients with primary ONSM treated with hypofractionated stereotactic radiotherapy (HF-SRT). Methods: Data of 36 patients treated with HF-SRT between 2008 and 2019 were retrospectively collected. The clinical target volume (CTV) was equal to the gross tumor volume and a 2 mm was added for the planning target volume. All responses other than progression were accepted as local control (LC). The VA grading was performed under 3 groups to provide an even distribution; 20/400 or worse, 20/40-20/400, and 20/40 or better. Results: Median HF-SRT dose was 25 Gy and the median CTV was 1.94 cc. After a median of 106 months of follow-up, the tumor regressed in 23 (64%), was stable in 9 (25%), and progressed in 4 (11%) eyes. The overall rate of LC was 89% with 2-, 5-, 10-, and 15-year rate of 100%, 94%, 84%, and 84%, respectively. Treatment-related late toxicity rate was 11%. The VA was stable in 27 (75%) eyes, improved in 5 (14%) eyes, and worsened in 4 (11%) eyes, respectively, after HF-SRT. Female gender was the only independent predictor of an improved VA. Conclusions: Hypofractionated stereotactic radiotherapy is a safe and satisfactory treatment option for primary ONSM without severe toxicity. It may be advisable to commence treatment before an established visual deficit of 20/400 or worse occurs, to make the most of the functional benefit.

Stereotactic Body Radiotherapy as an Effective Treatment for Pancreatic Cancer.

Background Stereotactic body radiotherapy (SBRT) allows the delivery of an ablative radiation dose to the tumor with minimal toxicity. Although magnetic resonance imaging (MRI)-guided SBRT appears to be a promising approach in the modern era, X-ray image-guided SBRT is still used worldwide for pancreatic cancer. This study aims to evaluate the results of X-ray image-guided SBRT in patients with locally advanced pancreatic cancer (LAPC). Methodology Medical records of 24 patients with unresectable LAPC who underwent X-ray image-guided SBRT between 2009 and 2022 were retrospectively evaluated. SPSS version 23.0 (IBM Corp., Armonk, NY, USA) was utilized for all analyses. Results The median age was 64 years (range = 42-81 years), and the median tumor size was 3.5 cm (range = 2.7-4 cm). The median total dose of SBRT was 35 Gy (range = 33-50 Gy) in five fractions. After SBRT, 30% of patients showed complete and 41% showed partial response, whereas 20% had stable disease and 9% had progression. Median follow-up was 15 months (range = 6-58 months). During follow-up, four (16%) patients had local recurrence, one (4%) had a regional recurrence, and 17 (70%) had distant metastasis (DM). The two-year local control (LC), local recurrence-free survival (LRFS), overall survival (OS), and DM-free survival (DMFS) rate was 87%, 36%, 37%, and 29%, respectively. In univariate analysis, a larger tumor size (>3.5 cm) and higher cancer antigen 19-9 level (>106.5 kU/L) significantly decreased the OS, LRFS, and DMFS rates. No severe acute toxicity was observed. However, two patients had severe late toxicity as intestinal bleeding. Conclusions X-ray image-guided SBRT provides a good LC rate with minimal toxicity for unresectable LAPC. However, despite modern systemic treatments, the rate of DM remains high which plays a major role in survival.

Multi-institutional study on the role of post-operative radiotherapy in elderly patients with endometrial cancer.

OBJECTIVE: To investigate the prognostic factors for survival and toxicities in elderly (≥65 years) patients with endometrial cancer who underwent post-operative radiotherapy. Additionally, to compare the treatment outcomes between the older elderly (≥75 years) and younger elderly (65-74 years) patients. METHODS: Medical records of patients with enometrial cancer treated between January 1998 and July 2019 were reviewed. Patients with stage IA to IIIC2, all histology subtypes, and any grade were included. All patients underwent total abdominal hysterectomy and received adjuvant radiotherapy with or without chemotherapy. All but 67 (8.4%) of 801 patients had lymph node dissection. Clinicopathological factors and treatment strategies were compared between the two age groups. The prognostic factors for overall survival and progression-free survival were investigated. RESULTS: A total of 801 patients with enometrial cancer, 627 patients (78.3%) younger elderly and 174 patients (21.7%) in the older elderly group were included. Median follow-up was 74.3 months (range 0.4-224.6). The older elderly patients had significantly higher rates of grade 3 tumors (51.7% vs 40.8%; p=0.04), cervical glandular involvement (21.8% vs 14.0%; p=0.03), and cervical stromal invasion (34.5% vs 27.9%; p=0.04) than the younger elderly patients. The rates of lymph node dissection (p=0.2), radiotherapy modalities (p=0.92), and systemic chemotherapy (p=0.2) did not differ between the two groups. The 5-year locoregional control and distant metastasis rates were 88.3% and 23.8%, respectively. The 5-year cause-specific survival and progression-free survival rates for younger and older elderly patients, were 79.8% vs 74.3% (p=0.04) and 67.5% vs 57.8% (p<0.001), respectively. In multivariate analysis, larger tumor size, non-endometrioid histology, cervical stromal involvement, and stage III disease were associated with poor cause-specific survival and progression-free survival. Age was an independent predictor of worse progression-free survival, but not of cause-specific survival. There was no significant difference in acute and late gastrointestinal and genitourinary toxicities between age groups. CONCLUSIONS: Post-operative radiotherapy for elderly patients with endometrial cancer is effective and well tolerated. Advanced age should not preclude appropriate treatment, especially in those with adequate quality of life, life expectancy, and functional status.

Stereotactic Radiotherapy for Adrenal Metastases: A Multi-Institutional Review of Patient Characteristics and Outcomes - Turkish Society for Radiation Oncology SBRT Group Study (Trod SBRT 10-004).

INTRODUCTION: This study aimed to report the outcomes of stereotactic body radiotherapy (SBRT) for adrenal metastasis in a retrospective multi-institutional cohort. METHODS: The outcomes of 124 patients with 146 adrenal metastases who underwent SBRT within 11 years (2008-2019) were retrospectively evaluated. Survival outcomes were analyzed by the Kaplan-Meier method. Patient, tumor, and treatment characteristics and their effects on survival, local control (LC), and toxicity outcomes were analyzed by log-rank and multivariate Cox regression methods. RESULTS: The median age was 60 years. The most frequent primary tumor site was the lung, followed by the gastrointestinal system and breast. The adrenal gland was the only metastatic site in 49 (40%) patients. Median biologically effective dose (BED)10 was 61 Gy. The overall LC rate was 83%, and it was positively correlated with the BED10 and fraction dose. The 1- and 2-year local recurrence-free survival, overall survival (OS), and progression-free survival (PFS) rate was 79% and 69%, 83% and 60%, and 31% and 12%, respectively. OS significantly improved with non-lung cancer and <4-cm lesion and PFS with a fraction dose ≥8 Gy, BED10 >65 Gy, and an isolated adrenal metastasis. Fourteen patients reported an acute toxicity, and late toxicity was observed in 3 patients, including one grade 5. CONCLUSION: A satisfactory LC rate was achieved for adrenal metastasis via SBRT. A higher BED10 and fraction dose were positive prognostic factors for tumor control. However, the main problem is DM in these patients, and systemic treatment options are needed to be improved.

The impact of serum albumin-to-alkaline phosphatase ratio in cervical cancer patients treated with definitive chemoradiotherapy.

We retrospectively analysed the prognostic significance of serum albumin, alkaline phosphatase (ALP) and albumin to ALP ratio (AAPR) and other prognostic factors affecting the overall survival (OS) and progression-free survival (PFS) in 200 cervical cancer patients treated with definitive chemoradiotherapy (CRT). The prognostic factors for OS and DFS, in addition to the predictive factors of albumin, ALP and AAPR, were investigated. Older age, lymph node metastasis, non-complete response (CR) to treatment and low serum albumin levels emerged as predictors of poor OS and PFS in multivariate analysis. However, with a cut-off value of 0.51, AAPR was not a significant prognostic factor of survival in multivariable analysis. There were no significant differences in clinicopathological factors between patients with low and high AAPR, except for lymph node metastasis, where lymph node metastasis rate was significantly higher in patients with a low AAPR compared to those with a high AAPR. Patients with CR had a significantly higher serum albumin level and AAPR compared to patients without CR. The pre-treatment serum albumin level was independent predictive for survival; therefore, it could be a suitable biomarker to guide systemic therapy and predict patient outcomes. Impact StatementWhat is already known on this subject? Two major determinants of tumour progression are nutritional status and inflammation. The albumin-to-alkaline phosphatase ratio (AAPR), which was originally proposed as a marker for nutritional status and immune response, was recently discovered to be a prognostic factor for various cancer types. However, its utility in the treatment of cervical cancer has not been established.What do the results of this study add? Low serum albumin levels were associated with a significantly shorter OS and PFS in cervical cancer patients treated definitively with CRT. AAPR, on the other hand, was not a significant prognostic factor for survival with a cut-off value of 0.51. Regional lymph node metastasis was significantly more common in patients with a low AAPR than in those with a high AAPR.What are the implications of these findings for clinical practice and/or further research? Patients with multiple clinicopathological risk factors and low serum albumin levels had an increased risk of disease recurrence and a poorer prognosis, highlighting the importance of additional adjuvant treatment strategies in these patients. Due to the preliminary nature of our findings, additional research is required to corroborate them.

Stereotactic body radiotherapy boost in patients with cervical cancer.

Our aim was to evaluate the oncological outcomes of stereotactic body radiotherapy (SBRT) boost in patients with cervical cancer. The data of 21 patients who received SBRT boost after definitive radiotherapy (RT) or chemoradiotherapy (CRT) between March 2012 and April 2019 were retrospectively evaluated. External beam radiotherapy (EBRT) was applied to patients with a total dose of 50.4 Gy in 28 fractions. Kaplan-Meier method was used for survival analysis (IBM SPSS 23 software) and p < .05 value was considered significant. After definitive RT or CRT, there was a complete response in 9 (43%) patients, partial response in 11 (52%) patients and stable disease in 1 (5%) patient. The median follow-up period was 28 months (range, 7.5-88 months). Two-years cancer-specific survival rate was 80%. While 2-year LC rate was 75% in patients with residual tumour size <4 cm, it was 50% when there was ≥4 cm residual tumour after definitive CRT (p = .1). The treatment was well-tolerated and no acute or late toxicity was observed. Although brachytherapy (BRT) is an essential part of the treatment in locally advanced cervical cancer, SBRT may be used in patients with small residual disease who are not candidate for BRT. IMPACT STATEMENTCervical cancer is one of the most common cancers in the world, and external beam radiotherapy (EBRT) and brachytherapy (BRT) are the main treatment options. However, in rare cases where BRT is not feasible, it has been questioned whether stereotactic body radiotherapy (SBRT) as an alternative to BRT.What is already known on this subject? Nowadays, BRT still appears to be the gold standard treatment. However, studies with a small number of patients and short follow-up periods in the literature show that SBRT can be a good alternative in cases where BRT cannot be performed.What do the results of this study add? Our study is one of the series with the largest number of patients in the literature and with the longest follow-up period. In this area where there is no prospective study, we think that retrospective data with high patient numbers are enlightening.What are the implications of these findings for clinical practice and/or further research? Our study shows that SBRT is an alternative option in cases with small residual disease where BRT cannot be applied, and it provides a basis for a prospective randomised study.

Uterine papillary serous and clear cell carcinomas: Comparison of characteristics and clinical outcomes.

INTRODUCTION: To assess the rate of disease control and survival after adjuvant treatment in patients with uterine papillary serous (PSC) and clear cell carcinoma (CCC) and compare the results between these two subtypes. METHODS: The medical charts of 199 patients with de novo uterine PSC or CCC who underwent radiotherapy (RT) following surgery between 2001 and 2019 in three radiation oncology departments were retrospectively evaluated. Adjuvant treatment was decided by a multidisciplinary tumor board. All patients were planned to undergo adjuvant 4-6 cycles of chemotherapy with external beam RT (EBRT) and/or vaginal brachytherapy (VBT). RESULTS: Median age was 63 years for all, 64 years for PSC, and 59 years for CCC, respectively. Complete surgical staging was applied in 98% of patients. Histopathologic subtype was PSC in 142 (71%) and pure CCC in 57 (29%) patients, respectively. FIGO stage was I in 107 (54%), II in 35 (18%), and III in 57 (28%) patients, respectively. Lympho-vascular space invasion and positive peritoneal cytology (PPC) were present in 42% and 10% of patients, respectively. All patients but 23 (12%) underwent adjuvant chemotherapy. Median follow-up was 49.5 months for all patients, 43.9 months for patients with PSC, and 90.4 months for patients with CCC, respectively. During follow-up, 20 (10%) patients developed pelvic recurrence (PR) and 37 (19%) developed distant metastasis (DM). PSC subtype increased the PR and DM rates, although the latter not statistically significant. The 5-year overall survival and disease-free survival rate was 73% and 69% for all patients, 71% and 66% for patients with PSC, and 77% and 75% for patients with CCC, respectively. The difference was more prominent in patients with stage ≥ IB disease. In multivariate analysis, advanced age and PPC significantly decreased all survival rates. CONCLUSION: PSC has a worse prognosis than CCC with regard to pelvic and distant recurrence with a trend for decreased survival rates. Therefore, a more aggressive therapy is needed for patients with uterine PSC, particularly in patients with stage ≥ IB disease.

Turkish translation and validation of the Xerostomia Inventory.

Objectives: The Xerostomia Inventory (XI) was developed to assess the severity of dryness in patients with xerostomia. It has a long and a short form with three- and five-point Guttman-type response options. In this study, we aimed to translate the XI into Turkish, to assess the validity and reliability of both response options in patients with head & neck cancer (HNC) or Sjögren syndrome (SS), and to select the optimal version for Turkish patients. Patients and methods: Between January 2019 and June 2019, the XI was translated into Turkish (XI-T) and applied to patients aged ≥18 years with HNC and SS. All patients were applied two tests including both the three- and five-point options. The internal consistency was assessed by Cronbach alpha and test-retest reliability by intraclass correlation coefficients (ICCs). Content validity was based on expert opinion and patient reviews. Results: A total of 186 patients (109 males, 77 females; median age: 54 years; range, 19 to 78 years) answered the XI-T. The number of patients with HNC and SS was 143 (77%) and 43 (23%), respectively. Median XI-T score was 17 for the three-point, and 24 for the five-point option, respectively. Overall internal consistency was satisfactory for both options (α=0.81 and α=0.89, respectively). Overall test-retest reliability was satisfactory and ICCs ranged between 0.71 and 0.92 for the three-point, and 0.36 and 0.94 for the five-point option, respectively. Assessments based on expert opinions and patient reviews also favored the content validity of the scale. Conclusion: The XI-T with both three- and five-point options is a valid and reliable tool to evaluate the presence and severity of dryness in patients with HNC and SS who experience xerostomia. The three-point option is more comprehensible and can be preferred over the five-point option in the Turkish population.

Do grape and black mulberry molasses have an effect on oral mucositis and quality of life in patients with head and neck cancer?

OBJECTIVE: We aimed to investigate the effect of black mulberry and grape molasses on the prevention and treatment of oral mucositis and quality of life (QoL) in patients with head and neck cancer (HNC). METHODS: Patients treated for HNC between 2010 and 2018 in our department were divided into three groups (group 1 = control (n = 14), group 2 = grape molasses (n = 40), and group 3 = black mulberry molasses (n = 40)). Oral mucositis, pain scoring, and weight loss were evaluated weekly. The European Organization for Research and Treatment of Cancer (EORTC) General QoL Questionnaire (QLQ-C30) and EORTC Head and Neck Cancer QoL Module (QLQ-HN35) were used to evaluate QoL. RESULTS: The mean body weight, scores of oral mucositis, and pain were similar among the groups throughout the treatment. Both groups 2 and 3 were associated with improved outcomes for swallowing, opening mouth, and weight loss in the EORTC HN35, and these parameters were not significantly different between groups 2 and 3. Global health score was higher in group 3 at the 6th week of RT compared to that of group 2. Both groups 2 and 3 had improved scores for role functioning, emotional and social functioning, fatigue, appetite loss, and pain throughout the treatment compared to group 1. CONCLUSIONS: Both grape and black mulberry molasses improved the QoL in HNC patients. No significant difference between black mulberry and grape molasses was found with regard to the healing of oral mucositis.

Does Combined Fractionated Stereotactic Radiotherapy and Immunotherapy Change the Outcome of Recurrent High-Grade Gliomas?

Background Radiotherapy (RT) with immune checkpoint inhibitors (ICI) has yielded good responses in many cancers. We aimed to report the results of combined fractionated stereotactic radiotherapy (FSRT) and ICI in patients with recurrent high-grade glioma. Methodology Patients were treated with FSRT and nivolumab which were continued until progression or toxicity. The Response Assessment in Neuro-oncology and Immunotherapy Response Assessment in Neuro-oncology criteria were used to assess treatment response on magnetic resonance imaging. Treatment-related toxicity was noted in all patients. Results A total of eight patients were included. Recurrence was detected after a median of 5.8 months following the first RT, all in the treatment field. FSRT (3 × 8 Gy) was applied with neoadjuvant, concurrent, and adjuvant nivolumab. After a median follow-up of 21.3 months from diagnosis and 12.6 months from recurrence, one patient was alive and seven succumbed to the disease. The median overall survival was 20.9 months after diagnosis and 12.9 months after recurrence. The median progression-free interval was 2.3 months after FSRT. The local control (LC) rate was 62.5% with a median local recurrence-free survival of nine months. Progression in other regions of the brain was observed in four patients with a median progression-free survival of 2.1 months. Acute toxicity was not observed. ICI-related grade 3 late pneumonitis was observed in two patients, and grade 1 late thyroid toxicity in two patients. One patient with pneumonitis also developed osteoporosis and radiation necrosis. Conclusions A high LC rate was achieved with concurrent FSRT and ICI with a severe late toxicity rate of 25%. This combination can be an option in recurrent high-grade gliomas.

Outcome and safety analysis of endometrial cancer patients treated with postoperative 3D-conformal radiotherapy or intensity modulated radiotherapy.

BACKGROUND: We sought to analyze the toxicity rates and the treatment outcomes in endometrial cancer (EC) patients treated with postoperative three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). MATERIAL AND METHODS: The clinical data of 646 EC patients treated with postoperative adjuvant 3DCRT (265 patients, 41%) or with IMRT (381 patients, 59%) between April 2007 and August 2019 were retrospectively analyzed. The primary endpoints were treatment-related acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. The secondary endpoints were LC and overall survival (OS) and disease-free survival (DFS). RESULTS: Median follow-up time was 37 months. The rates for acute GI and GU toxicities of any grade for the entire group were 55.6% and 46.8%, respectively. Acute grade ≥2 GI toxicity was significantly less in patients treated with IMRT compared to those treated with 3DCRT (11.0% vs. 19.2%, p=.004). However, no significant difference grade ≥2 GU toxicities was observed between the 3DCRT and IMRT groups (15.1% vs. 11.0%; p=.15). Acute grade ≥2 GI and GU toxicities were higher in patients receiving systemic chemotherapy, while paraaortic field irradiation increases only the risk of acute grade ≥2 GI toxicity. Estimated 3-year late grade ≥3 GI toxicity rates in the 3DCRT- and IMRT-treated patients were 4.6% and 1.9% (p= .03), respectively. The patients treated with adjuvant ChT had higher rates of late serious GI complications than those without adjuvant ChT. No significant difference in terms of survival and disease control was observed between the 3DCRT and IMRT treatment groups. No significant factor for LC was found in the multivariate analysis. CONCLUSION: In this multicentric study involving one of largest patient population, we found that IMRT-treated EC patients showed comparable clinical outcomes but with a lower incidence of GI toxicities compared with those treated with 3DCRT.