Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

PURPOSE: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era. METHODS: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT. RESULTS: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5­year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10. CONCLUSIONS: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.

Nimotuzumab-containing regimen for pediatric diffuse intrinsic pontine gliomas: a retrospective multicenter study and review of the literature.

PURPOSE: Nimotuzumab is an IgG1 antibody that targets epidermal growth factor receptor (EGFR). Overexpression of EGFR is detected in some pediatric brain tumors including diffuse intrinsic pontine gliomas (DIPG)s. METHODS: Since May 2010, nimotuzumab, combined with carboplatin or vinorelbine or Temozolomide (TMZ), was administered during progressive disease (PD) after the use of the institutional protocol consisting of radiotherapy (RT) + TMZ and adjuvant TMZ. After May 2012, children with newly diagnosed disease received TMZ during RT, and nimotuzumab and TMZ after RT. Nimotuzumab was given as 150 mg/m2/dose once a week for 12 weeks, and then every other week with TMZ until PD. PD patients were switched to nimotuzumab + vinorelbine combination until death. RESULTS: Nimotuzumab was used in 24 children with DIPG (seven in the PD group, 17 in the newly diagnosed patient group). In the PD group, median survival time was 12 months (7-42 months); 1-year and 2-year overall survival (OS) rates were 42.9 ± 18% and 14.3 ± 13%, respectively. The median survival in this group, after the initiation of nimotuzumab was 6 months (3-8 months). In the newly diagnosed patient group, median survival time was 11 months (3-35 months) and median progression free survival was 4 months (1-21 months). The 1-year OS in this group was 35.3 ± 11% and 2 year OS was 11.8 ± 7%. Nimotuzumab ± chemotherapy was well tolerated with no major adverse effect. CONCLUSION: Nimotuzumab-containing regimens are feasible and tolerable; it might be that some patients either with newly diagnosed DIPG or with progressive disease may benefit modestly from nimotuzumab-containing combinations.

Efficacy of the VIT (vincristine, irinotecan and temozolomide) regimen in adults with metastatic Ewing sarcoma.

The goal of the research was to investigate if a combination of vincristine, irinotecan and temozolomide (VIT) could benefit adult patients with metastatic Ewing sarcoma who had already been heavily pretreated. Metastatic Ewing sarcoma patients had their data retrospectively analyzed. The patients' clinical, radiological and therapeutic data were recorded. Survival analyzes were performed with these data. The study enlisted the participation of sixteen patients. The average age was 25 years old (range: 20-42). The lung was the most prevalent metastatic location (81.3%). Patients had received at least two distinct chemotherapy combinations (87.5%) and palliative radiotherapy (37.5%) before receiving the (VIT) combination. The Median progression-free survival time was found as 3.4 (95% CI, 1.8-4.9) months. Five patients (31.3%) experienced a partial response, while the remaining patients (68.7%) had progressing disease. Thirteen individuals (81.3%) had grade 1-2 adverse events, whereas five (31.3%) had grade 3-4 adverse events. Hematological complications were the most common side effects (87.5%). Median overall survival was calculated as 5.6 (95% CI, 3.6-7.5) months in the patients after the beginning of VIT regimen. We demonstrated the efficacy of the VIT regimen in adult patients with metastatic Ewing sarcoma in this research. In these extensively pretreated patients, toxicities were a concern. Metastatic Ewing sarcoma patients have few treatment choices. In patients who have had a good performance status, VIT regimen may be considered for disease control.

Clinical course and features of soft tissue sarcomas in geriatric patients: a single-center experience.

OBJECTIVE: This study was performed to examine the disease course in geriatric patients with soft tissue sarcoma and determine the risk factors for mortality. METHODS: We retrospectively analyzed patients who were treated at Istanbul University Oncology Institute from January 2000 to August 2021. RESULTS: Eighty patients were included in the study. The patients' median age was 69 years (range, 65-88 years). The median overall survival of patients diagnosed between the ages of 65 and 74 years was 70 months, and that of patients diagnosed at the age of ≤75 years was significantly lower at 46 months. The median survival of patients who did and did not undergo surgical resection was 66 and 11 months, respectively, with a significant difference. The median overall survival of patients with positive and negative surgical margins was 58 and 96 months, respectively, also with a significant difference. Age at diagnosis and recurrence/metastasis significantly affected mortality. A 1-year increase in the age at diagnosis increased mortality by 1.147 times. CONCLUSION: Age of >75 years, inability to undergo surgery, positive surgical margins, and head and neck location may be associated with a poor prognosis in geriatric patients with soft tissue sarcoma.

Outcomes and prognostic factors in metastatic renal cell carcinoma patients with brain metastases.

BACKGROUND: To evaluate the outcomes and prognostic factors in patients with brain metastatic renal cell carcinoma (bmRCC). METHODS: The data of 322 patients with metastatic renal cell carcinoma, taken between 2012 and 2020, were retrospectively reviewed. Overall survival (OS) and prognostic factors were evaluated with Kaplan-Meier analysis and Cox regression analysis. RESULTS: Forty (12.4%) of the patients had bmRCC. Seventeen (42.5%) of the patients were de novo metastatic, and nine (22.5%) of the patients had brain metastases at presentation. Twenty-four (60%) patients previously had received various therapies (tyrosine kinase inhibitor or checkpoint inhibitors). After brain metastases developed, 35 (87.5%) of the patients received brain radiotherapy (whole-brain radiotherapy or stereotactic radiosurgery), and twenty-five (62.5%) patients received different systemic therapies. Nine patients received sunitinib, nine received pazopanib, five received nivolumab, and two received axitinib. The median OS was 8.8 months (range: 2.9-14.6) for all patients with bmRCC. In univariate analysis, the number of brain metastasis (P = 0.35), the site of brain metastasis (left, right or bilateral) (P = 0.79), the largest size of brain metastasis (P = 0.45), the number of extracranial metastatic sites (P = 0.81), de novo metastatic disease (P = 0.17), primary tumor site (left or right) (P = 0.90), and tumor grade (P = 0.09) were not statistically significant factors on OS. However, age (P = 0.02), a history of nephrectomy (P < 0.001), receiving brain radiotherapy (P = 0.005), and type of systemic treatment (P = 0.04) were statistically significant. Only, the effect of brain radiotherapy on OS (P = 0.01) was confirmed in multivariate analysis. CONCLUSIONS: In this study, we observed that the prognosis of patients with bmRCC was poor. Despite a small number of patients, we detected that the effect of tyrosine kinase inhibitors and nivolumab was comparable, and receiving brain radiotherapy was a prognostic factor for OS.

Childhood Rhabdomyosarcoma of the Female Genital Tract: Association with Pathogenic DICER1 Variation, Clinicopathological Features, and Outcomes.

STUDY OBJECTIVE: Rhabdomyosarcomas (RMSs) of the female genital tract (FGT) have been recently shown to be associated with germline pathogenic variation in DICER1, which can underlie a tumor predisposition disorder. We sought to determine the incidence of a pathogenic variation in DICER1 in a cohort of RMSs of the FGT, as well as to evaluate the clinicopathological features and outcomes of the patients. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We retrospectively reviewed medical records of the patients diagnosed with RMS of the FGT between 1990 and 2019. Molecular genetic sequencing of the tumor to detect an RNase IIIb domain hot spot mutation in DICER1 samples was performed in 7 patients. Individuals with a missense mutation in the tumor were also screened for a loss of function germline mutation in DICER1. RESULTS: Of 210 cases of pediatric RMS, 11 arose from the FGT. Molecular genetic sequencing of the tumor samples revealed a somatic missense mutation in the RNase IIIb domain of DICER1 in a total of 3 patients, 2 patients with embryonal RMS of the cervix/uterus, and 1 patient with ovarian embryonal RMS. As a result of genetic testing for the loss of function germline mutation in DICER1, a heterozygous pathogenic variant was also found in 2 of these patients. CONCLUSION: Despite the limited number of patients, our findings suggest that it is important to be aware of the possible association between RMS of FGT and pathogenic germline DICER1 variants because the detection of this mutation in a patient or relatives can provide the opportunity for surveillance of related conditions that might improve long-term outcomes and survival.

Osteosarcoma of the rib: A rare presentation.

In children and adolescents with chest pain and dyspnea, pneumonia, pleural effusion, and empyema are the frequent causes in the differential diagnosis. Malignant tumors of the chest wall are rare and most originate from the ribs. In children, the most frequent malignant tumor of the rib is Ewing's sarcoma. Osteosarcomas of the rib are very rare. Osteosarcoma has a predilection for rapidly growing long bones including the femur, tibia and humerus in adolescents. In this paper, we present an adolescent girl who presented with chest pain and dyspnea with osteosarcoma that originated from the rib and extended to the right hemithorax.

Primary Rhabdomyosarcoma of the Breast: Imaging Findings and Literature Review.

BACKGROUND: Primary breast rhabdomyosarcoma (RMS) can occur in children. There is a lack of knowledge regarding radiologic findings and added diffusion-weighted magnetic resonance imaging (MRI) features of RMS in the literature. CASE REPORT: A 12-year-old girl was diagnosed with primary alveolar RMS of the breast. Gray scale ultrasound revealed posterior acoustic enhancement behind a well-circumscribed, multilobulated hypoechoic mass. Doppler ultrasound revealed increased peripheral and central vascularity. Hypointense septations on T2-weighted image exhibiting more enhancement than the stroma on late gadolinium-enhanced images were striking within a hyperintense mass. A hyperintense hemorrhagic focus on T1-weighted image was present in the absence of any necrosis. Avid enhancement on early postcontrast images proceeding from the periphery to the center was depicted. CONCLUSION: A rapidly enlarging mass with an echogenic peripheral rim together with posterior acoustic enhancement on gray scale ultrasound, intense vascularity on Doppler ultrasound, axillary lymphadenopathy, and satellite nodules on MRI should raise suspicion. Enhancing central and peripheral septations are suggestive of RMS. Dynamic contrast-enhanced MRI in suspected cases can provide valuable data in the differential diagnosis.

Neoadjuvant radiotherapy for myxoid liposarcomas: Oncologic outcomes and histopathologic correlations.

OBJECTIVE: The aim of this study was to evaluate the histopathological features of primary extremity myxoid liposarcoma before and after neoadjuvant radiation therapy, and to evaluate the oncological outcomes of the patients. METHODS: The study included 23 patients (16 men and 7 women with a mean age of 43 (24-69) years) with primary myxoid liposarcoma of the extremities, who were treated between January 1998 and December 2015. Inclusion criteria were histopathological confirmation of the diagnosis with both the initial biopsy and the resection specimen, and having undergone neoadjuvant radiotherapy. Demographic, clinical and histopathological data were evaluated. RESULTS: Over a mean follow-up time of 55.2 (8-139) months, 5 patients (21.7%) died secondary to disease progression, leaving 18 patients (78.3%) still alive at the time of last follow-up. Only one patient (4%) experienced local recurrence and six (26%) patients developed distant metastases. Disease-free survival at 5 and 10 years were 66%; whereas, overall patient survival at 5 and 10 years were 78.1% and 71.0%, respectively. Tumor size (>15 cm) and presence of metastasis were significantly associated with increased overall mortality. On histopathology, necrosis was present in 12/23 resection specimens. Hyalinization/fibrosis and residual viable tumor was present in all specimens. Adipocytic maturation/cytodifferentiation was seen in 8/23 patients. CONCLUSION: Neoadjuvant radiotherapy was effective for myxoid liposarcomas histopathologically, although these histopathological features did not affect the patients' oncological outcomes. Favorable oncological outcomes were obtained with neoadjuvant radiotherapy, surgical resection and chemotherapy. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer.

AIM: To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga68-PSMA PET/CT in patients with recurrent PCa. METHODS: A total of 109 consecutive patients (median age 71 years; range 48-89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented. RESULTS: In 91(83.4%) patients at least one lesion characteristic for PCa was detected by68Ga-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2-640) ng/ml.There was a significant difference between 68Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative 68Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative 68Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911-0.993). CONCLUSIONS: 68Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and 68Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive 68Ga-PSMA PET/CT results.

Conventionally Fractionationed Volumetric Arc Therapy versus Hypofractionated Stereotactic Body Radiotherapy: Quality of Life, Side Effects, and Prostate-Specific Antigen Kinetics in Localized Prostate Cancer.

OBJECTIVES: To compare conventionally fractionationed volumetric arc therapy (VMAT) and hypofractionated stereotactic body radiotherapy (SBRT) modalities in terms of prostate-specific antigen (PSA) kinetics, toxicity, and quality of life (QOL) in patients with localized prostate cancer. METHODS: Patients received radical radiotherapy as either 33.5 Gy/5 fr for SBRT or 75.6 Gy/35 fr for VMAT. International Prostate Symptom Score (IPSS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (QLQ-PR25) forms were used to assess QOL. RESULTS: Of the 48 patients (28 in SBRT and 20 in VMAT) included in the study, 40 (20 in SBRT and 20 in VMAT) were evaluated for QOL status. PSA control rate was 100% and PSA nadir value was 0.5 ng/dl in both arms during the median follow-up period of 23 months. The magnitude of PSA bounce was higher in the SBRT arm than in the VMAT arm (P = 0.01). The PSA decline rate in the VMAT arm was higher than in the SBRT arm (P = 0.028). Three (10.7%) patients treated with SBRT who had a history of transurethral resection of the prostate (TURP) experienced grade 3 urinary toxicity. No significant difference was observed concerning sexual activity and sexual functioning scores, whereas scores at 10.5 and 13.5 months were decreased in both arms. The SBRT and VMAT arms had similar urinary incontinence, bowel symptoms, and IPSS obstruction scores. The magnitude of increase in IPSS scores at treatment completion was higher in the VMAT arm than in the SBRT arm (P = 0.046). The decrease in hormonal symptom scores at 4.5, 10.5, and 13.5 months was higher in the VMAT arm than in the SBRT arm (P = 0.007, 0.027, and 0.021, respectively). CONCLUSIONS: Both treatment modalities had similar effectiveness and provided acceptable outcomes in terms of toxicity and QOL. Grade 3 urinary toxicities might be eliminated with careful patient selection for SBRT.

Ovarian ablation by radiation therapy: is it still an option for the ablation of ovarian function in endocrine responsive premenopausal breast cancer patients?

Surgical or medical ovarian ablation is likely to be the treatment of choice at the current time, radiation ablation (RA) can be still a reasonable alternative. The efficacy and toxicity of radiation therapy (RT) for ovarian function suppression in 118 premenopausal breast cancer patients were retrospectively evaluated. The median age was 39 years (range 21-52 years). RT was given with either Co-60 or 15MV photons of the linear accelerator. The median total dose was 15Gy in 4 consecutive fractions (range 5Gy single fraction-36Gy in 18 fractions over 3.5 weeks). The endpoint for treatment efficacy was menstrual status. Amenorrhea was noted in 113 of 118 patients (96%) in 6 months following RA. Five patients (4%) who had still normal menstrual functioning after 6 months of RA underwent estradiol and follicle stimulating hormone measurements and were found to have premenopausal levels. No acute Grade 3 or 4 (according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria) toxicities were noted. With a median follow-up of 24.5 months (range: 6-167), no late severe complications that could be attributable to RT were reported. RA should be considered as an option for endocrine responsive premenopausal breast cancer patients and can be easily delivered when postoperative or palliative irradiation is given.