Decrease in treatment intensity predicts worse outcome in patients with locally advanced head and neck squamous cell carcinoma undergoing radiochemotherapy

PURPOSE: Radiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications. METHODS: To investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018. RESULTS: During RCT, 77 (41%, 95% CI 34-49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = < 0.001), and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88), respectively. CONCLUSIONS: Reductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy

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

\ua9 2022 The Authors. 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

Pulmonary Stereotactic Body Radiation Therapy of Oligometastatic Head-and-Neck Squamous Cell Carcinoma: A Multicenter Retrospective Study

PURPOSE The value of stereotactic body radiation therapy (SBRT) in patients with oligometastatic head-and-neck squamous cell carcinoma (HNSCC) remains unclear, as existing evidence is primarily derived from retrospective single-center analyses with small patient cohorts. This study aimed to evaluate the outcomes of pulmonary SBRT in patients with oligometastatic HNSCC and to identify factors associated with survival. METHODS AND MATERIALS This trinational multicenter cohort study, including 16 centers from Germany, Austria, and Switzerland, retrospectively analyzed patients with oligometastatic HNSCC undergoing SBRT for pulmonary metastases between 2010 and 2023. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival and incidence of local failures. RESULTS A total of 178 patients with 284 irradiated lung metastases were analyzed. The most common primary HNSCC subsites were oropharyngeal (n = 71), laryngeal (n = 37), and hypopharyngeal (n = 31). Lung metastases were treated with a median biologically effective dose (BED$_{α/β}$$_{=}$$_{10 Gy}$) of 105 Gy (IQR, 84-113) at the planning target volume periphery. After a median follow-up of 40 months (95% CI, 34-46), the median OS and progression-free survival were 33 months (95% CI, 26-40) and 9 months (95% CI, 7-11), respectively. The 1-year cumulative incidence of local failures was 5.5% (95% CI, 3.2-8.8). One patient (0.6%) developed acute grade 3 dysphagia, and among 146 patients assessed for chronic toxicities, 2 (1.4%) experienced grade 3 events, with no grade 4-5 toxicities. On multivariable analysis, older (>65 years) patients (hazard ratio [HR], 1.59; 95% CI, 1.02-2.49; P = .040) and females (HR, 1.76; 95% CI, 1.04-2.99; P = .035) exhibited worse OS, whereas longer time between HNSCC diagnosis and first SBRT was associated with longer OS (HR, 0.99; 95% CI, 0.99-1.00; P = .045). CONCLUSION SBRT for pulmonary metastases achieves excellent local control with minimal toxicity in patients with oligometastatic HNSCC. Prospective trials are needed to determine the optimal timing for integrating SBRT with systemic treatment

Damage analysis for flexible pavements at high and low temperatures using visco-elastic hybrid finite element method (FEM)

This paper describes stress and deformation analysis for different damage in flexible pavement at high and low temperature using hybrid visco-elastic FEM and relaxation test results in tension for bituminous mixtures, which were performed at different temperatures. Cracking due to thermal load and rutting are a big concern in flexible pavement. But, recently, many researchers had been reported that longitudinal cracking under wheel path at high temperature occurred. This cracking never occurred in surface pavement covered by overbridge in summer. We tried to analyze the cause of longitudinal cracking under wheel path at high temperature and thermal stress in flexible pavement at low temperature using hybrid visco-elastic FEM. This paper consists of experiment of relaxation modulus for bituminous mixtures taken from fields and stress analysis using hybrid visco-elastic FEM. Apparatus in order to measure relaxation modulus was modified in our laboratory. It was concluded that longitudinal cracking was caused by large shearing force due to radial tire of automobiles at high temperature and thermal stresses due to thermal load were almost the same for both rutting and longitudinal cracking sections in Swiss.6th international RILEM Symposium on Performance Testing and Evaluation of Bituminous Materials (PTEBM'03). 2003. Zurich

RILEM Interlaboratory Test on Pavement Performance Prediction and Evaluation

The former RILEM TC 182 PEB organized 1997 an international inter-laboratory test on pavement performance, prediction and evaluation. The aim was to predict the expected damages after 10 years on the basis of traffic and climatic data. Two sections in Austria and Portugal were constructed and test samples were cut from the pavement and send to the different laboratories. 13 laboratories of 12 countries participated in the study and gave performance predictions according their own methods and standards. The report which summarizes the results in detail is available on the RILEM web site. RILEM TC 206 ATB TG 4 continued the long term observation. Unfortunately, only the Austrian section in Villach could be monitored as planned, since the Portuguese section had problems in the data supply. In 2007 the Austrian road administration stopped the observation of the test section in Villach. The paper summarises the actual road condition and compares it to the predicted performance.</p