Predictive value of health-related quality of life on radiotherapy-related toxicities in patients with head and neck cancer.

PURPOSE: Little is known about whether baseline health-related quality of life (HRQoL) scores also could predict occurrence radiotherapy-related toxicities, which we aim to assess in this study. METHODS: This study analyzed data from 200 patients enrolled in randomized study investigating the utility of HRQoL. HRQOL was assessed at baseline and during follow up using QLQ-C30 questionnaire and major toxicity was considered as adverse event ≥ 3 according to NCI-CTCAE classification. Cox regressions adjusting for clinical and sociodemographic data were used to assess prognostic significance of HRQOL scores. RESULTS: In multivariable analyses adjusted on clinical and sociodemographic data, every 10-point improvement in physical (HR = 0.74), role (HR = 0.87) and social (HR = 0.88) functioning was associated with 24%, 13% and 12% lower hazard of occurrence of major toxicity respectively while every 10 point-increase in dyspnea (HR = and loss appetite was associated with 15% and 16% increased hazard of major toxicity. CONCLUSION: Certain baseline HRQoL scores were found to be significantly associated with the occurrence of major toxicity.

Randomized Trial Assessing the Impact of Routine Assessment of Health-Related Quality of Life in Patients with Head and Neck Cancer.

The impact of routine assessment of health-related quality of life (HRQoL) on satisfaction with care and the HRQoL of patients with head and neck cancer (HNC) treated with radiotherapy was assessed. Patients with HNC were randomly assigned to two arms, with stratification on sex, cancer localization, and stage of the disease. In the intervention arm, the patients completed the EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires first before randomization, then before each medical appointment during radiotherapy (7 weeks), and then every 3 months until 1 year and at 2 years thereafter. In the control arm, the EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires were completed before randomization and at 1 year and 2 years thereafter. The primary endpoint was mean change in HRQoL at score at 2 years from baseline assessed by EQ VAS from the EuroQol questionnaire. The secondary endpoint was mean change in satisfaction with care at 2 years from baseline assessed by QLQ-SAT32. Two hundred patients with head and neck cancers were involved in this study (mean age, 58.83 years (range, 36.56-87.89)), of whom 100 were assigned to the intervention arm and 100 to the control arm. Patients in the intervention arm were reported to have a statistically significant increase in EQ VAS at 2 years (p < 0.0001) and exceeded the minimal clinically important difference (mean change at 2 years from baseline = 10.46). In the two arms, mean differences between arms were not statistically significant, but minimal clinically important differences in favor of the intervention arm were found for EQ VAS (mean change difference (MD) = 5.84), satisfaction with care, in particular waiting times (MD = 10.85) and satisfaction with accessibility (MD = 6.52). Routine assessment of HRQoL improves HRQoL and satisfaction with care for patients with HNC treated with radiotherapy.

Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.

BACKGROUND: Chemoradiotherapy is the standard of care for unresected locally advanced squamous cell carcinoma of the head and neck. We aimed to assess if addition of avelumab (anti-PD-L1) to chemoradiotherapy could improve treatment outcomes for this patient population. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 study, patients were recruited from 196 hospitals and cancer treatment centres in 22 countries. Patients aged 18 years or older, with histologically confirmed, previously untreated, locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity (unselected for PD-L1 status), an Eastern Cooperative Oncology Group performance status score of 0 or 1, and who could receive chemoradiotherapy were eligible. Patients were randomly assigned (1:1) centrally by means of stratified block randomisation with block size four (stratified by human papillomavirus status, tumour stage, and nodal stage, and done by an interactive response technology system) to receive 10 mg/kg avelumab intravenously every 2 weeks plus chemoradiotherapy (100 mg/m2 cisplatin every 3 weeks plus intensity-modulated radiotherapy with standard fractionation of 70 Gy [35 fractions during 7 weeks]; avelumab group) or placebo plus chemoradiotherapy (placebo group). This was preceded by a single 10 mg/kg avelumab or placebo lead-in dose given 7 days previously and followed by 10 mg/kg avelumab or placebo every 2 weeks maintenance therapy for up to 12 months. The primary endpoint was progression-free survival by investigator assessment per modified Response Evaluation Criteria in Solid Tumors, version 1.1, in all randomly assigned patients. Adverse events were assessed in patients who received at least one dose of avelumab or placebo. This trial is registered with ClinicalTrials.gov, NCT02952586. Enrolment is no longer ongoing, and the trial has been discontinued. FINDINGS: Between Dec 12, 2016, and Jan 29, 2019, from 907 patients screened, 697 patients were randomly assigned to the avelumab group (n=350) or the placebo group (n=347). Median follow-up for progression-free survival was 14·6 months (IQR 8·5-19·6) in the avelumab group and 14·8 months (11·6-18·8) in the placebo group. Median progression-free survival was not reached (95% CI 16·9 months-not estimable) in the avelumab group and not reached (23·0 months-not estimable) in the placebo group (stratified hazard ratio 1·21 [95% CI 0·93-1·57] favouring the placebo group; one-sided p=0·92). The most common grade 3 or worse treatment-related adverse events were neutropenia (57 [16%] of 348 patients in the avelumab group vs 52 [15%] of 344 patients in the placebo group), mucosal inflammation (50 [14%] vs 45 [13%]), dysphagia (49 [14%] vs 47 [14%]), and anaemia (41 [12%] vs 44 [13%]). Serious treatment-related adverse events occurred in 124 (36%) patients in the avelumab group and in 109 (32%) patients in the placebo group. Treatment-related deaths occurred in two (1%) patients in the avelumab group (due to general disorders and site conditions, and vascular rupture) and one (<1%) in the placebo group (due to acute respiratory failure). INTERPRETATION: The primary objective of prolonging progression-free survival with avelumab plus chemoradiotherapy followed by avelumab maintenance in patients with locally advanced squamous cell carcinoma of the head and neck was not met. These findings may help inform the design of future trials investigating the combination of immune checkpoint inhibitors plus CRT. FUNDING: Pfizer and Merck KGaA, Darmstadt, Germany.

Drastic Reduction of Turnaround Time After Implementation of a Fully Automated Assay for RAS-BRAF Mutations in Colorectal Cancer: A Pilot Prospective Study in Real-life Conditions.

In some situations, there is a need for rapid mutation tests for guiding clinical decisions and starting targeted therapies with minimal delays. In this study we evaluated the turnaround time before and after the implementation of a fully automated multiplex assay for KRAS and NRAS/BRAF mutation tests (Idylla™ platform, Biocartis) in metastatic colorectal cancer. The objective of this project was to compare the turnaround times in 2017-2018 with the fully automated multiplex assay to the 2016 results with previous methods. Centers with a number of tests for metastatic colorectal cancer > 100 yearly and a usual turnaround time ≥ 3 weeks for mutation detection were selected. Results of 505 KRAS tests and 369 NRAS/BRAF tests were transmitted by 10 centers. The mean turnaround time from test prescription to reception of results was reduced from 25.8 days in 2016 to 4.5 days in 2017-2018. In conclusion, this pilot project shows that the Idylla™ platform for testing KRAS and NRAS/BRAF mutations allows an optimized turnaround time from test prescription to reception of results.

Can Comprehensive Geriatric Assessment Predict Tolerance of Radiotherapy for Localized Prostate Cancer in Men Aged 75 Years or Older?

Curative radiotherapy for prostate cancer is common in the elderly. However, concerns about potential toxicity have inhibited access to radiotherapy for this population, for whom preserving quality of life (QoL) is crucial. The primary endpoint was to identify predictors of impaired QoL in men aged 75 years or older treated with curative intent radiotherapy with or without androgen deprivation therapy (ADT) for localized prostate cancer. We prospectively performed comprehensive geriatric assessment (CGA) and administered QoL questionnaires to 208 elderly (>75 years) patients prior to, plus two and six months after, radiotherapy (NCT02876237). The median age of the patients was 77 years (range 75-89). At the start of the study, comorbidities were highlighted in 65% of patients: 23% were depressed, 23% had cognitive impairment, and 16% had reduced independence. At six months, 9% of patients had a consistently decreased QoL (>20 points), and a further 16% had a more moderate reduction (10 to 20 points) in QoL. None of the parameters studied (tumor characteristic, treatment, or oncogeriatric parameters) were predictive of a reduced QoL following radiotherapy. Though co-existing geriatric impairment was common, QoL was maintained for 75% of patients six months after radiotherapy. CGA was poorly predictive of tolerance of prostatic radiotherapy. Geriatric assessments dedicated to quality of life following radiotherapy need to be developed.

Comprehensive Geriatric Assessment and quality of life after localized prostate cancer radiotherapy in elderly patients.

INTRODUCTION: Radiotherapy can diminish quality of life (QoL) for prostate cancer patients. Our objective was to evaluate the effect of radiotherapy on QoL in men aged 75 years or older treated with radiotherapy for a localized prostate cancer, and to identify predictors of reduced QoL. PATIENTS AND METHODS: We prospectively administered a battery of geriatric (MNA, GDS, Get up and Go Test, CIRS-G, ADL, IADL, MMSE), toxicity (IPSS; IIEF 5), and QoL (QLQ C30) screening tests in 100 elderly patients before and two months after prostate cancer radiotherapy (NCT 02876237). Patients ≥ 75 years undergoing radiotherapy with a curative intent for localized prostate cancer with or without androgen deprivation therapy (ADL) were eligible for study inclusion. Correlations between patient-assessed QoL and tumor characteristics, radiotherapy treatment or CGA parameters were sought using the Fisher or the Mann and Whitney tests. Changes in QoL parameters over time were analyzed using the Wilcoxon signed-rank test. RESULTS: At study entry, scores for IADL impairments were present in 51%, reduced autonomy in activities of daily living in 16%, cognitive impairment found in 20%, depression-related symptoms in 31%, and 66% of patients had significant co-morbidities. Eight percent were judged to be at risk of fall and 2% were found to be undernourished. Severely impaired (IPSS ≥ 20) urinary function was observed in 11.2% and 13.5% of patients before and two months after completion of radiotherapy respectively. Significantly decreased QoL (> 20 points) at two months after treatment was found in 13% of patients and a moderate but clinically relevant reduction (10 to 20 points) in 17% of patients. No tumor characteristic, treatment, or oncogeriatric parameter was predictive of reduced QoL following prostate cancer radiotherapy. CONCLUSION: Despite sometimes markedly diminished oncogeriatric parameters, prostate cancer radiotherapy was generally well tolerated in these elderly patients. We found no predictive factor to determine which patients would experience impaired quality of life following radiotherapy.

Stereotactic Body radiation therapy for liver tumors with or without rotational intensity modulated radiation therapy.

BACKGROUND: To evaluate the feasibility and efficacy of Stereotactic body radiation therapy (SBRT) for primary liver lesions and liver metastases treated with linear accelerators with or without rotational Intensity Modulated RadioTherapy (IMRT). METHODS: Patients with either hepatocellular carcinoma, cholangiocarcinoma or metastatic liver lesions who had one to three lesions treated with SBRT in a single institution were retrospectively reviewed. Tumor response was evaluated according to EASL criteria 3 months after SBRT completion using MRI and/or abdominal CT scan. Responses were categorised as: Stable Disease (SD), Partial Response (PR), Complete Response (CR), Local Progression or Distant Progression in cases of new intra-hepatic lesions out-of-field or extra-hepatic metastases. Local Control (LC), Progression Free Survival (PFS), Overall Survival (OS) and treatment-related toxicities are reported. RESULTS: Between 2007 and 2012, 20 patients with a total of 24 lesions were treated with SBRT. Fourteen patients presented hepatocellular carcinoma (HCC), the others had either metastatic lesions from colorectal cancer (CRC) or cholangiocarcinoma. The median diameter of the lesions was 23 mm (5-98).The dose per fraction ranged from 6 to 20 Gy with a median total dose of 60 Gy (range: 36-60 Gy). The dose was prescribed to the 80% isodose line covering the PTV.The median follow-up was 24 months (15.7-29.7).The actuarial LC rate was 78% for patients with HCC and 83% for those with adenocarcinoma and cholangiocarcinoma. Median OS was 37 months and OS rates were 83% at 12 and 24 months for HCC and 100% for adenocarcinoma. PFS was 54% for HCC and 50% for other types of tumors at 24 months.Acute grade 3-4 toxicities occurred in 2 patients; a small proportion of the other patients experienced grade 1 or 2 toxicities. CONCLUSIONS: SBRT provides excellent local control with minimal side effects in selected patients.

Exclusive image guided IMRT vs. radical prostatectomy followed by postoperative IMRT for localized prostate cancer: a matched-pair analysis based on risk-groups.

BACKGROUND: To investigate whether patients treated for a localized prostate cancer (PCa) require a radical prostatectomy followed by postoperative radiotherapy or exclusive radiotherapy, in the modern era of image guided IMRT. METHODS: 178 patients with PCa were referred for daily exclusive image guided IMRT (IG-IMRT) using an on-line 3D ultra-sound based system and 69 patients were referred for postoperative IMRT without image guidance after radical prostatectomy (RP + IMRT). Patients were matched in a 1:1 ratio according to their baseline risk group before any treatment. Late toxicity was scored using the CTV v3.0 scale. Biochemical failure was defined as a postoperative PSA ≤ 0.1 ng/mL followed by 1 consecutive rising PSA for the postoperative group of patients and by the Phoenix definition (nadir + 2 ng/mL) for the group of patients treated with exclusive radiotherapy. RESULTS: A total of 98 patients were matched (49:49). From the start of any treatment, the median follow-up was 56.6 months (CI 95% = [49.6-61.2], range [18.2-115.1]). No patient had late gastrointestinal grade ≥ 2 toxicity in the IG-IMRT group vs. 4% in the RP + IMRT group. Forty two percent of the patients in both groups had late grade ≥ 2 genitourinary toxicity. The 5-year FFF rates in the IG-IMRT group and in the RP + IMRT groups were 93.1% [80.0-97.8] and 76.5% [58.3-87.5], respectively (p = 0.031). CONCLUSIONS: Patients with a localized PCa treated with IG-IMRT had better oncological outcome than patients treated with RP + IMRT. Further improvements in postoperative IMRT using image guidance and dose escalation are urgently needed.