Patterns of Disease Progression and Outcome of Patients With Testicular Seminoma Who Relapse After Adjuvant or Curative Radiation Therapy.

PURPOSE: Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy. METHODS AND MATERIALS: Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse. RESULTS: With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression. CONCLUSIONS: Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy.

Can Pre-Treatment Inflammatory Parameters Predict the Probability of Sphincter-Preserving Surgery in Patients with Locally Advanced Low-Lying Rectal Cancer?

There is evidence suggesting that pre-treatment clinical parameters can predict the probability of sphincter-preserving surgery in rectal cancer; however, to date, data on the predictive role of inflammatory parameters on the sphincter-preservation rate are not available. The aim of the present cohort study was to investigate the association between inflammation-based parameters and the sphincter-preserving surgery rate in patients with low-lying locally advanced rectal cancer (LARC). A total of 848 patients with LARC undergoing radiotherapy from 2004 to 2019 were retrospectively reviewed in order to identify patients with rectal cancer localized ≤6 cm from the anal verge, treated with neo-adjuvant radiochemotherapy (nRCT) and subsequent surgery. Univariable and multivariable analyses were used to investigate the role of pre-treatment inflammatory parameters, including the C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for the prediction of sphincter preservation. A total of 363 patients met the inclusion criteria; among them, 210 patients (57.9%) underwent sphincter-preserving surgery, and in 153 patients (42.1%), an abdominoperineal rectum resection was performed. Univariable analysis showed a significant association of the pre-treatment CRP value (OR = 2.548, 95% CI: 1.584-4.097, p < 0.001) with sphincter preservation, whereas the pre-treatment NLR (OR = 1.098, 95% CI: 0.976-1.235, p = 0.120) and PLR (OR = 1.002, 95% CI: 1.000-1.005, p = 0.062) were not significantly associated with the type of surgery. In multivariable analysis, the pre-treatment CRP value (OR = 2.544; 95% CI: 1.314-4.926; p = 0.006) was identified as an independent predictive factor for sphincter-preserving surgery. The findings of the present study suggest that the pre-treatment CRP value represents an independent parameter predicting the probability of sphincter-preserving surgery in patients with low-lying LARC.

Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma - A Report From the HIT 2000 Trial.

PURPOSE: We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. METHODS AND MATERIALS: Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols were applied. Genetically defined tumor entity (former molecular subgroup) was available for 157 patients. RESULTS: Median follow-up time was 7.3 (range, 0.09-13.86) years. There was no difference between HIT SIOP PNET 4 trial patients and observational patients outside the randomized trial, with 7 years progression-free survival rates (PFS) of 79.5% ± 3.1% versus 78.7% ± 3.1% (P = .62). On univariate analysis, the time interval between surgery and irradiation (≤ 48 days vs ≥ 49 days) showed a strong trend to affect PFS (80.4% ± 2.2% vs 64.6% ± 9.1%; P = .052). Furthermore, histologically and genetically defined tumor entities and the extent of postoperative residual tumor influenced PFS. On multivariate analyses, a genetically defined tumor entity wingless-related integration site-activated vs non-wingless-related integration site/non-SHH, group 3 hazard ratio, 5.49; P = .014) and time interval between surgery and irradiation (hazard ratio, 2.2; P = .018) were confirmed as independent risk factors. CONCLUSIONS: Using a centralized review program and risk-stratified therapy for all patients registered to the study center, outcome was identical for patients with nonmetastatic medulloblastoma treated on and off the randomized HIT SIOP PNET 4 trial. The prognostic values of prolonged time to RT and genetically defined tumor entity were confirmed.

The decreased mean platelet volume is associated with poor prognosis in patients with oropharyngeal cancer treated with radiotherapy.

BACKGROUND: There is considerable evidence that platelets contribute to cancer growth and metastatic dissemination. In recent studies, altered mean platelet volume (MPV) has been associated with prognosis in different types of cancer. However, the prognostic role of the MPV in head and neck squamous cell cancer (HNSCC) is currently discussed controversially. The present study was performed to analyze and further elucidate the prognostic significance of the MPV in HNSCC. METHODS: A total of 319 oropharyngeal squamous cell cancer (OPSCC) patients treated with radiotherapy at a tertiary academic center were enrolled in the present study. Kaplan-Meier method as well as uni- and multivariate Cox proportional hazards were used to evaluate the impact of MPV on cancer-specific survival (CSS), locoregional control (LC) and recurrence-free survival (RFS). RESULTS: The median MPV was 10.30 fL (mean 10.26 ± 1.17fL). Univariate analyses showed a significant association of the MPV with CSS (HR 0.85, 95% CI 0.74-0.98, p = 0.025), LC (HR 0.86, 95% CI 0.74-0.99, p = 0.034) and RFS (HR 0.87, 95% CI 0.76-0.996; p = 0.043). In multivariate analysis, the MPV remained an independent prognostic factor for CSS (HR 0.77, 95% CI 0.63-0.93, p = 0.008), LC (HR 0.80, 95% CI 0.65-0.98, p = 0.030), and RFS (HR 0.83, 95% CI 0.685-0.999, p = 0.049). CONCLUSIONS: Our findings indicate that the MPV is a prognostic marker in OPSCC patients and may contribute to future individual risk assessment.

The AST/ALT (De Ritis) Ratio Predicts Survival in Patients with Oral and Oropharyngeal Cancer.

Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are strongly involved in cancer cell metabolism and have been associated with prognosis in different types of cancer. The purpose of the present study was to evaluate the prognostic significance of the pre-treatment AST/ALT ratio in a large European cohort of patients with oral and oropharyngeal squamous cell cancer (OOSCC). Data from 515 patients treated for OOSCC at a tertiary academic center from 2000-2017 were retrospectively analyzed. Levels of AST and ALT were measured prior to the start of treatment. Uni- and multivariate Cox regression analyses were applied to evaluate the prognostic value of the AST/ALT ratio for cancer-specific survival (CSS) and overall survival (OS), survival rates were calculated. Univariate analyses showed a significant association of the AST/ALT ratio with CSS (hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.38-2.12; p < 0.001) and OS (HR 1.69, 95% CI 1.41-2.02; p < 0.001). In multivariate analysis, the AST/ALT ratio remained an independent prognostic factor for CSS and OS (HR 1.45, 95% CI 1.12-1.88, p = 0.005 and HR 1.42, 95% CI 1.14-1.77, p = 0.002). Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the AST/ALT ratio was 1.44, respectively. In multivariate analysis, an AST/ALT ratio > 1.44 was an independent prognostic factor for poor CSS and OS (HR 1.64, 95% CI 1.10-2.43, p = 0.014 and HR 1.55, 95% CI 1.12-2.15; p = 0.008). We conclude that the AST/ALT ratio is a prognostic marker for survival in OOSCC patients and could contribute to a better risk stratification and improved oncological therapy decisions.

The Elevated Pre-Treatment C-Reactive Protein Predicts Poor Prognosis in Patients with Locally Advanced Rectal Cancer Treated with Neo-Adjuvant Radiochemotherapy.

The aim of the present study was to investigate the association of the pre-treatment C-reactive protein (CRP) plasma level with survival outcomes in a cohort of 423 consecutive patients with locally advanced rectal cancer treated with neo-adjuvant radiochemotherapy followed by surgical resection. To evaluate the prognostic value of the CRP level for clinical endpoints recurrence-free survival (RFS), local-regional control (LC), metastases-free survival (MFS), and overall survival (OS), uni- and multivariate Cox regression analyses were applied, and survival rates were calculated using Kaplan-Meier analysis. The median follow-up time was 73 months. In univariate analyses, the pre-treatment CRP level was a significant predictor of RFS (hazard ratio (HR) 1.015, 95% CI 1.006-1.023; p < 0.001), LC (HR 1.015, 95% CI 1.004-1.027; p = 0.009), MFS (HR 1.014, 95% CI 1.004-1.023; p = 0.004), and OS (HR 1.016, 95% CI 1.007-1.024; p < 0.001). Additionally, univariate analysis identified the MRI circumferential resection margin (mrCRM) and pre-treatment carcinoembryonic antigen (CEA) as significant predictor of RFS (HR 2.082, 95% CI 1.106-3.919; p = 0.023 and HR 1.005, 95% CI 1.002-1.008; p < 0.001). Univariate analysis also revealed a significant association of the mrCRM (HR 2.089, 95% CI 1.052-4.147; p = 0.035) and CEA (HR 1.006, 95% CI 1.003-1.008; p < 0.001) with MFS. Age and CEA were prognostic factors for OS (HR 1.039, 95% CI 1.013-1.066; p = 0.003 and HR 1.005, 95% CI 1.002-1.008; p < 0.001). In multivariate analysis that included parameters with a p-level < 0.20 in univariate analysis, the pre-treatment CRP remained a significant prognostic factor for RFS (HR 1.013, 95%CI 1.001-1.025; p = 0.036), LC (HR 1.014, 95% CI 1.001-1.027; p = 0.031), and MFS (HR 1.013, 95% CI 1.000-1.027; p = 0.046). The results support the hypothesis that an elevated pre-treatment CRP level is a predictor of poor outcome. If confirmed by additional studies, this easily measurable biomarker could contribute to the identification of patients who might be candidates for more aggressive local or systemic treatment approaches or the administration of anti-inflammatory drugs.

The Pre-Treatment C-Reactive Protein Represents a Prognostic Factor in Patients with Oral and Oropharyngeal Cancer Treated with Radiotherapy.

The purpose of the present study was to evaluate the prognostic significance of the pre- treatment C-reactive protein (CRP) level in a cohort of 503 patients with oral and oropharyngeal cancer treated at a tertiary academic center between 2000 and 2017. Cancer-specific survival (CSS), overall survival (OS) and loco-regional control (LC) were calculated using Kaplan-Meier analysis. To evaluate the prognostic value of the CRP level for the clinical endpoints, univariate and multivariate Cox regression models were applied. The median follow-up period was 61 months. Patients were divided into elevated CRP (≥5 mg/L) and normal CRP groups, according to pre-treatment plasma levels. An increased CRP level was significantly associated with shorter CSS (p < 0.001, log-rank test), as well as with shorter OS (p < 0.001, log-rank test) and loco-regional control (p = 0.001, log-rank test). In addition, multivariate analysis identified CRP as an independent predictor for CSS (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.08-2.35; p = 0.020) as well as for OS (HR 1.62, 95%CI 1.17-2.24; p = 0.004) and LC (HR 1.50, 95%CI 1.06-2.14; p = 0.023). In subgroup analysis, Kaplan Meier curves revealed that an elevated pre-treatment CRP level was a consistent prognostic factor for poor CSS (p = 0.003, log-rank test), OS (p = 0.001, log-rank test), and LC (p = 0.028, log-rank test) in patients treated with definitive (chemo-) radiotherapy, whereas a significant association in patients undergoing surgery and postoperative radiotherapy was not detected. The pre-treatment CRP level seems to represent a prognostic factor for CSS, OS, and LC in patients with oral and oropharyngeal cancer, particularly in those treated with definitive (chemo-) radiotherapy. Additional large-scale prospective studies are warranted to confirm and extend our findings.

Treatment results of radiation therapy for muscle-invasive bladder cancer.

PURPOSE: To assess local control and survival rates in patients with muscle-invasive bladder cancer treated with external-beam radiotherapy and to investigate prognostic factors. PATIENTS AND METHODS: Between 1997 and 2007, 75 patients (male, n = 58; female, n = 17, median age, 74.2 years) with localized transitional cell carcinoma of the bladder (T2, n = 34; T3, n = 32; T4, n = 9) not suitable for radical surgery due to advanced age, comorbidity or inoperability underwent external-beam radiotherapy without simultaneous chemotherapy at the University Clinic of Therapeutic Radiology and Oncology, Medical University of Graz, Austria. A conformal four-field technique was used in all patients to treat the tumor and regional lymph nodes with single daily fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy, followed by a cone-down to encompass the empty bladder which was boosted to 70-70.4 Gy. All patients had undergone transurethral tumor resection prior to radiotherapy which was macroscopically incomplete in 62 patients. RESULTS: Complete response was achieved in 65% of patients. Actuarial 3-year local control and metastases-free survival rates were 52.5% and 63.7%, 3-year local recurrence-free survival rate in complete responders was 71%. In univariate analysis, hydronephrosis, lymph vessel invasion, and macroscopic residual tumor were significantly predictive of disease progression. Hydronephrosis and lymph vessel invasion were also associated with a higher risk of local recurrence. The actuarial 3-year progression-free and overall survival rates were 40.1% and 56.9%, respectively. CONCLUSION: Radiotherapy is an effective treatment option in terms of local control and survival even in elderly patients with locally advanced bladder cancer not suitable for cystectomy.