Long-term health-related quality of life in head and neck cancer survivors: A large multinational study.

Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.

Meningeal Solitary Fibrous Tumor: A Single-Center Retrospective Cohort Study.

Background: Meningeal solitary fibrous tumors (SFTs) are rare, malignant, mesenchymal tumors of the central nervous system. While surgical gross total resection is widely accepted as a positive prognostic factor for local control (LC), the role of postoperative radiotherapy (PORT) remains controversial. We sought to report our institutional experience with a particular focus on outcomes after PORT. Materials and Methods: In this single-center, retrospective cohort study, 20 patients with the primary diagnosis of histopathologically confirmed meningeal SFT were analyzed. Data on patient characteristics, imaging, treatment modalities, histopathology, and oncological outcomes were collected. LC and overall survival (OS) were assessed using the Kaplan-Meier estimator. Results: The median follow-up time was 95.8 months. After surgery only, 9 out of 11 patients (81.8%) developed a local recurrence while, after surgery and PORT, 3 out of 9 patients (33.33%) showed local failure. The 5- and 10-year LC rates were 50.5% and 40.4% in the surgery-only group and 80% at both time points in the surgery with the PORT group. In the surgery-only group, 4 out of 11 patients (36.4%) died, and 4 out of 9 patients (44.4%) died in the surgery and PORT group. OS rates after 5 and 10 years were 88.9% and 66.7% in the surgery-only group and 88.9% and 76.2% in the surgery with PORT group. Conclusions: Our findings suggest that PORT may improve LC in patients with meningeal SFT. The low incidence of meningeal SFT impedes prospective studies and requires further international collaborative efforts to exploit retrospective datasets and molecular analysis to improve patient outcomes.

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation.

PURPOSE: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. METHODS AND MATERIALS: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine-Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). CONCLUSIONS: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.

Postoperative adjuvant radiochemotherapy with cisplatin versus adjuvant radiochemotherapy with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma- the study protocol of the Adrisk trial.

Most of the patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. Standards of care for curative-intent treatment of this patient group are either surgery and adjuvant radio(chemo)therapy (aRCT) or definitive chemoradiation. Despite these treatments, especially pathologically intermediate and high-risk HNSCC often recur. The ADRISK trial investigates in locally advanced HNSCC and intermediate and high risk after up-front surgery if the addition of pembrolizumab to aRCT with cisplatin improves event-free sur-vival compared to aRCT alone. ADRISK is a prospective, randomized controlled investiga-tor-initiated (IIT)-phase II multicenter trial within the German Interdisciplinary Study Group of German Cancer Society (IAG-KHT). Patients with primary resectable stage III and IV HNSCC of the oral cavity, oropharynx, hypopharynx and larynx with pathologic high (R1, extracapsular nodal extension) or intermediate risk (R0 <5 mm; N≥2) after surgery will be eligible. Two hun-dred forty patients will be randomly assigned (1:1) to either standard aRCT with cisplatin (standard arm) or aRCT with cisplatin + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months) (interventional arm). Endpoints are event-free and overall survival. Recruitment started in August 2018 and is ongoing.

Subgroup Analysis of Overall Survival among Smoking and Non-Smoking Elderly Patients with HNSCC.

Smoking is a leading cause of head and neck squamous cell carcinoma (HNSCC). However, non-smokers are also affected by HNSCC, and the prognostic factors applicable to older non-smokers with HNSCC are largely unknown. The aim of this study was to determine predictors of overall survival (OS) in patients both with and without a smoking history aged 70 and over at initial diagnosis. Retrospective data of patients aged ≥70 (initial diagnoses 2004-2018) were examined. Evaluated predictors included tumour stage, biological age, health and therapy. A total of 688 patients (520 smokers, 168 non-smokers) were included with a median age of 74. The 5-year OS was 39.6%. Non-smokers had significantly improved OS compared to smokers (52.0% versus 36.0%, p < 0.001). Disease-free survival (DFS) differed significantly between both groups (hazard ratio = 1.3; 95%CI 1.04-1.626). TNM stage and the recommended therapies (curative versus palliative) were comparable. The proportion of p16-positive oropharyngeal carcinomas was significantly higher in non-smokers (76.7% versus 43.8%, p < 0.001). Smokers were significantly more likely to be men (p < 0.001), drinkers (p < 0.001), and have poorer health status (Karnofsky performance status, KPS, p = 0.023). They were also more likely to have additional tumours (p = 0.012) and lower treatment adherence (p = 0.038). Important predictors of OS identified in both groups, were, among others, alcohol abuse, KPS, Charlson comorbidity index, site of primary tumour, UICC stage and treatment received. Elderly non-smokers are also affected by HNSCC, however, both OS and DFS are increased compared to smokers.

Serious Long-Term Effects of Head and Neck Cancer from the Survivors' Point of View.

The long-term problems of head and neck cancer survivors (HNCS) are not well known. In a cross-sectional international study aimed at exploring the long-term quality of life in this population, 1114 HNCS were asked to state their two most serious long-term effects. A clinician recorded the responses during face-to-face appointments. A list of 15 example problems was provided, but a free text field was also available. A total of 1033 survivors responded to the question. The most frequent problems were 'dry mouth' (DM) (n = 476; 46%), 'difficulty swallowing/eating' (DSE) (n = 408; 40%), 'hoarseness/difficulty speaking' (HDS) (n = 169; 16%), and 'pain in the head and neck' (PHN) (n = 142; 14%). A total of 5% reported no problems. Logistic regression adjusted for age, gender, treatment, and tumor stage and site showed increased odds of reporting DM and DSE for chemo-radiotherapy (CRT) alone compared to surgery alone (odds ratio (OR): 4.7, 95% confidence interval (CI): 2.5-9.0; OR: 2.1, CI: 1.1-3.9), but decreased odds for HDS and PHN (OR: 0.3, CI: 0.1-0.6; OR: 0.2, CI: 0.1-0.5). Survivors with UICC stage IV at diagnosis compared to stage I had increased odds of reporting HDS (OR: 1.9, CI: 1.2-3.0). Laryngeal cancer survivors had reduced odds compared to oropharynx cancer survivors of reporting DM (OR: 0.4, CI: 0.3-0.6) but increased odds of HDS (OR: 7.2, CI: 4.3-12.3). This study provides evidence of the serious long-term problems among HNCS.

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy.

Importance: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. Objective: To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. Design, Setting, and Participants: The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. Interventions: All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. Results: Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). Conclusions and Relevance: In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.

Image-guided robotic radiosurgery for the treatment of arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are challenging lesions, often requiring multimodal interventions; however, data on the efficacy of stereotactic radiosurgery for cerebral AVMs are limited. This study aimed to evaluate the clinical and radiographic results following robotic radiosurgery, alone or in combination with endovascular treatment, and to investigate factors associated with obliteration and complications in patients with AVM. METHODS: We retrospectively analyzed the clinical and imaging characteristics of 123 patients with AVMs of all Spetzler-Martin grades treated at two institutions by robotic radiosurgery in single-fraction doses (CyberKnife). Embolization was performed before radiosurgery in a subset of patients to attempt to downgrade the lesions. Factors associated with AVM obliteration and complications (toxicity) were identified via univariate and multivariate analyses. RESULTS: The median follow-up time was 48.1 months (range, 3.6-123 months). Five patients were lost to follow-up. The obliteration rate in the 59 patients with a follow-up period exceeding four years was 72.8%. Complete obliteration and partial remission were achieved in 67 (56.8%) and 31 (26.3%) cases, respectively, whereas no change was observed in 20 cases (17.8%). Embolization was performed in 54/123 cases (43.9%). Complete and partial obliteration were achieved in 29 (55.7%) and 14 (26.9%) embolized patients, respectively. In the multivariate analysis, the factors associated with obliteration were age (p = .018) and the Spetzler-Martin grade (p = .041). Treatment-induced toxicity (radiation necrosis and/or edema) was observed in 15 cases (12.7%), rebleeding occurred in three cases (2.5%), and the rate of mortality associated with rebleeding was 1.7%. CONCLUSIONS: CyberKnife radiosurgery is a valid approach for treating AVMs of all Spetzler-Martin-grades, with satisfactory obliteration rates, low toxicity, and a relatively rare incidence of rebleeding.

18F-Fluorodeoxyglucose Positron Emission Tomography of Head and Neck Cancer: Location and HPV Specific Parameters for Potential Treatment Individualization.

Purpose: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is utilized for staging and treatment planning of head and neck squamous cell carcinomas (HNSCC). Some older publications on the prognostic relevance showed inconclusive results, most probably due to small study sizes. This study evaluates the prognostic and potentially predictive value of FDG-PET in a large multi-center analysis. Methods: Original analysis of individual FDG-PET and patient data from 16 international centers (8 institutional datasets, 8 public repositories) with 1104 patients. All patients received curative intent radiotherapy/chemoradiation (CRT) and pre-treatment FDG-PET imaging. Primary tumors were semi-automatically delineated for calculation of SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Cox regression analyses were performed for event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Results: FDG-PET parameters were associated with patient outcome in the whole cohort regarding clinical endpoints (EFS, OS, LRC, FFDM), in uni- and multivariate Cox regression analyses. Several previously published cut-off values were successfully validated. Subgroup analyses identified tumor- and human papillomavirus (HPV) specific parameters. In HPV positive oropharynx cancer (OPC) SUVmax was well suited to identify patients with excellent LRC for organ preservation. Patients with SUVmax of 14 or less were unlikely to develop loco-regional recurrence after definitive CRT. In contrast FDG PET parameters deliver only limited prognostic information in laryngeal cancer. Conclusion: FDG-PET parameters bear considerable prognostic value in HNSCC and potential predictive value in subgroups of patients, especially regarding treatment de-intensification and organ-preservation. The potential predictive value needs further validation in appropriate control groups. Further research on advanced imaging approaches including radiomics or artificial intelligence methods should implement the identified cut-off values as benchmark routine imaging parameters.

Three-Dimensional Evaluation of Isodose Radiation Volumes in Cases of Severe Mandibular Osteoradionecrosis for the Prediction of Recurrence after Segmental Resection.

BACKGROUND: Pre-operative margin planning for the segmental resection of affected bone in mandibular osteoradionecrosis (ORN) is difficult. The aim of this study was to identify a possible relation between the received RT dose, exposed bone volume and the progression of ORN after segmental mandibular resection. METHOD: Patients diagnosed with grade 3-4 ORN for which a segmental resection was performed were included in the study. Three-dimensional reconstructions of RT isodose volumes were fused with postoperative imaging. The primary outcome was the recurrence of ORN after segmental resection. Subsequently, RT exposed mandibular bone volumes were calculated and the location of the bone cuts relative to the isodose volumes were assessed. RESULTS: Five out of thirty-three patients developed recurrent ORN after segmental mandibular resection. All cases with recurrent ORN were resected inside an isodose volume of ≥56 Gy. The absolute mandibular volume radiated with 56 Gy was significantly smaller in the recurrent group (10.9 mL vs. 30.7 mL, p = 0.006), as was the proportion of the mandible radiated with 56 Gy (23% vs. 45%, p = 0.013). CONCLUSION: The volume of radiated bone was not predictive for risk of progression. The finding that recurrent ORN occurred with bone resection margins within the 56 Gy isodose volume suggests that this could serve as a starting point for the pre-operative planning of reducing the risk of ORN recurrence.

The Prognostic Significance of p16 and its Role as a Surrogate Marker for Human Papilloma Virus in Oral Squamous Cell Carcinoma: An Analysis of 281 Cases.

BACKGROUND/AIM: This study analyzed the expression of p16 in a large cohort of patients suffering from oral squamous cell carcinoma (OSCC) who received initial surgical therapy in order to evaluate the prognostic significance of p16 expression and to analyze its value as a surrogate marker to determine human papilloma virus (HPV) status. MATERIALS AND METHODS: Immunohistochemical staining of p16 was performed on tissue microarrays. Different expression levels of p16 (>25%; >50%; ≥70%) with a moderate to strong intensity were correlated with the clinical outcome. HPV DNA was analyzed by polymerase chain reaction (PCR). RESULTS: A total of 281 patients were included in this study. The p16 expression obtained using the abovementioned three different cutoffs did not significantly influence 5-year overall survival (OS) (p=0.23; p=0.45; p=0.23) nor recurrence-free survival (RFS) (p=0.79; p=0.45; p=0.142). In univariate Cox regression analysis, the p16 expression level was not a risk factor for OS (HR=0.637; 95%CI=0.271-1.5; p=0.300) and RFS (HR=0.74; 95%CI=0.339-1.61; p=0.449). A total of 17 patients (6.0%) were p16 positive with a cutoff ≥70%. HPV DNA was found in 4/11 of these cases by PCR, resulting in a positive predictive value of 0.36. In patients receiving adjuvant radio(chemo)therapy, a significantly (p=0.042) longer OS was observed in patients with p16 expression greater than 25% vs. ≤25%. CONCLUSION: In comparison with OPSCC, (strong) p16 positivity is rare in OSCC; however, in patients receiving primary surgery with adjuvant radio(chemo)therapy, p16 expression is associated with a higher survival rate. In conjunction with prior studies, p16 does not seem to be a reliable surrogate marker for HPV infection in OSCC.

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 2 with Recommendations on Psycho-oncology, Rehabilitation, Follow-up, Recurrence, Palliative Therapy and Healthcare Facilities.

Aim This is an update of the interdisciplinary S3-guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL), published in March 2021. The work on the updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process used to update the 2014 S3-guideline was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on the consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which would take account of more recently published literature and the recent appraisal of new evidence. Recommendations The short version of this guideline consists of recommendations and statements on palliative therapy and follow-up of patients with cervical cancer. The most important aspects included in this updated guideline are the new FIGO classification published in 2018, the radical open surgery approach used to treat cervical cancer up to FIGO stage IB1, and the use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.

Influence of Tumor Site on Survival in Young Patients with Head and Neck Squamous Cell Carcinoma.

The number of patients under the age of 45 diagnosed with head and neck squamous cell carcinomas (HNSCC) is increasing, probably due to the incidence of oropharyngeal cancers. Comparisons of HNSCC in young and old patients regarding tumor site and survival in sample sizes of relevance are rarely published. The aim of the study was to analyze the differences in survival between age groups dependent on tumor site and the influence of oropharyngeal cancers on the rising rates of HNSCC in the young. The records of 4466 patients diagnosed with HNSCC were reviewed retrospectively. Patients younger than 45 years were divided further into four subgroups for specific age differences in the young. The influences of patient and clinicopathological characteristics on survival were assessed using Kaplan-Meier analyses. Among the patient cohort, 4.8% were younger than 45 years. Overall survival (OS) in these patients was better, with a 5-year OS of 66.1% (vs. 46.4%), while relapse-free survival (RFS) was better in the older patient population, with a 5-year RFS of 74.9% (vs. 68.1%). Decreased RFS in the young was found for advanced tumor stages and tumor sited at the larynx. Hypopharynx and advanced stages were independent risk factors for OS under 45 years. Overall, 44.4% of all HNSCC in patients under 30 years were nasopharyngeal cancers, and incidence decreased with age. The incidence of oropharyngeal cancers increased significantly with age. Better OS in the young may be explained by lower tumor and disease stages, whereas oropharyngeal tumors and HPV were not found to cause rising rates of HNSCC. Laryngeal malignancies in young patients might be related to an increased malignant potential and should, consequently, be treated as such.

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 1 with Recommendations on Epidemiology, Screening, Diagnostics and Therapy.

Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process of updating the S3 guideline dating from 2014 was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on a consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which took account of more recently published literature and the appraisal of the new evidence. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, screening, diagnostic workup and therapy of patients with cervical cancer. The most important new aspects included in this updated guideline include the newly published FIGO classification of 2018, the radical open surgery approach for cervical cancers up to FIGO stage IB1, and use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.

Predictors for Adherence to Treatment Strategies in Elderly HNSCC Patients.

Finding a cure may be less important than ensuring the quality of life in elderly patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to determine predictors for adherence. Clinical and pathological data from patients ≥70 years with HNSCC (initial diagnoses 2004-2018) were investigated retrospectively. Evaluated clinical predictors included biological age (Charlson Comorbidity Index; CCI), patient health (Karnofsky Performance Status; KPS) and therapy data. A total of 1125 patients were included. The median age was 75 years, 33.1% reached CCI ≥ 6, and 53.7% reached KPS ≤ 70%. In total, 968 patients were adherent, whereas 157 were nonadherent. Nonadherent patients were significantly more often smokers (p = 0.003), frequent drinkers (p = 0.001), had a worse health status (p ≤ 0.001) and a lower biological age (p = 0.003), an advanced T classification and lymph node involvement or UICC stage (each p ≤ 0.001). Approximately 88.0% of the included patients received a curative treatment recommendation. A total of 6.9% discontinued the therapy, and 7.0% refused the therapy. With the increasing complexity of a recommended therapy, adherence decreased. The 5-year overall survival was significantly higher in adherent patients (45.1% versus 19.2%). In contrast to the chronological patient age, biological age is a significant predictor for adherence. The evaluated predictors for nonadherence need to be verified prospectively.

Total body irradiation as part of conditioning regimens in childhood leukemia-long-term outcome, toxicity, and secondary malignancies.

BACKGROUND: Total body irradiation (TBI) is an established part of conditioning regimens prior to stem cell transplantation in childhood leukemia but is associated with long-term toxicity. We retrospectively analyzed survival, long-term toxicity, and secondary malignancies in a pooled cohort of pediatric patients (pts.) treated with the same TBI regimen. METHODS: Analyzed were 109 pts. treated between September 1996 and November 2015. Conditioning treatment according to EBMT guidelines and the ALL SCTped 2012 FORUM trial consisted of chemotherapy (CT) and TBI with 2 Gy b.i.d. on 3 consecutive days to a total dose of 12 Gy. Median follow-up was 97.9 months (2-228 months). RESULTS: Overall survival (OS) in our cohort at 2, 5, and 10 years was 86.1, 75.5, and 63.0%, respectively. Median survival was not reached. Long-term toxicity developed in 47 pts. After chronically abnormal liver and kidney parameters in 31 and 7 pts., respectively, growth retardation was the most frequent finding as seen in 13 pts. Secondary malignancies were rare (n = 3). CONCLUSION: TBI-containing conditioning regimens in pediatric stem cell transplantation (SCT) are highly effective. Efforts to replace TBI- with CT-containing regimens have only been successful in subgroups of pts. Although we could show long-term toxicity in 43% of pts., overall survival was 63% at 10 years. Still, long-term effects such as growth retardation can permanently impact the pts.' quality of life and functioning. Along with new substances, efforts should be undertaken to optimize TBI techniques and accompany the treatment by systematic follow-up programs beyond 5 years to improve detection of rare events.

Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro.

Radiotherapy of head and neck squamous cell carcinoma can lead to long-term complications like osteoradionecrosis, resulting in severe impairment of the jawbone. Current standard procedures require a 6-month wait after irradiation before dental reconstruction can begin. A comprehensive characterization of the irradiation-induced molecular and functional changes in bone cells could allow the development of novel strategies for an earlier successful dental reconstruction in patients treated by radiotherapy. The impact of ionizing radiation on the bone-forming alveolar osteoblasts remains however elusive, as previous studies have relied on animal-based models and fetal or animal-derived cell lines. This study presents the first in vitro data obtained from primary human alveolar osteoblasts. Primary human alveolar osteoblasts were isolated from healthy donors and expanded. After X-ray irradiation with 2, 6 and 10 Gy, cells were cultivated under osteogenic conditions and analyzed regarding their proliferation, mineralization, and expression of marker genes and proteins. Proliferation of osteoblasts decreased in a dose-dependent manner. While cells recovered from irradiation with 2 Gy, application of 6 and 10 Gy doses not only led to a permanent impairment of proliferation, but also resulted in altered cell morphology and a disturbed structure of the extracellular matrix as demonstrated by immunostaining of collagen I and fibronectin. Following irradiation with any of the examined doses, a decrease of marker gene expression levels was observed for most of the investigated genes, revealing interindividual differences. Primary human alveolar osteoblasts presented a considerably changed phenotype after irradiation, depending on the dose administered. Mechanisms for these findings need to be further investigated. This could facilitate improved patient care by re-evaluating current standard procedures and investigating faster and safer reconstruction concepts, thus improving quality of life and social integrity.

Risks and Benefits of Fiducial Marker Placement in Tumor Lesions for Robotic Radiosurgery: Technical Outcomes of 357 Implantations.

Fiducial markers (FM) inserted into tumors increase the precision of irradiation during robotic radiosurgery (RRS). This retrospective study evaluated the clinical complications, marker migration, and motion amplitude of FM implantations by analyzing 288 cancer patients (58% men; 63.1 ± 13.0 years) who underwent 357 FM implantations prior to RRS with CyberKnife, between 2011 and 2019. Complications were classified according to the Society of Interventional Radiology (SIR) guidelines. The radial motion amplitude was calculated for tumors that moved with respiration. A total of 725 gold FM was inserted. SIR-rated complications occurred in 17.9% of all procedures. Most complications (32.0%, 62/194 implantations) were observed in Synchrony®-tracked lesions affected by respiratory motion, particularly in pulmonary lesions (46.9% 52/111 implantations). Concurrent biopsy sampling was associated with a higher complication rate (p = 0.001). FM migration occurred in 3.6% after CT-guided and clinical FM implantations. The largest motion amplitudes were observed in hepatic (20.5 ± 11.0 mm) and lower lung lobe (15.4 ± 10.5 mm) lesions. This study increases the awareness of the risks of FM placement, especially in thoracic lesions affected by respiratory motion. Considering the maximum motion amplitude, FM placement remains essential in hepatic and lower lung lobe lesions located >100.0 mm from the spine.

Effectiveness and Safety of Robotic Radiosurgery for Optic Nerve Sheath Meningiomas: A Single Institution Series.

The role of robotic radiosurgery (RRS) in the treatment of optic nerve sheath meningiomas (ONSM) remains controversial and it is only performed in specialized institutions due to tight dose constraints. We evaluated the effectiveness and safety of RRS in the management of ONSM. Twenty-five patients with 27 ONSM lesions who underwent RRS using the Cyberknife (CK) system were retrospectively analyzed (median age, 47.9 years; 84.0% women). Multisession RRS was used with 4-5 fractions with a cumulative dose of 20.0-25.0 Gy in 84.0% of patients and a single fraction at a dose of 14.0-15.0 Gy in 16% of patients. Prior to RRS, seven (28%) patients experienced blindness on the lesion side. In those patients with preserved vision prior to radiosurgery, the visual acuity remained the same in 90.0% and improved in 10.0% of the patients. Overall local tumor control was 96.0% (mean follow-up period; 37.4 ± 27.2 months). Neither patient age, previous surgery, or the period from the initial diagnosis to RRS showed a dependency on visual acuity before or after radiosurgery. RRS is a safe and effective treatment for the management of ONSM. Hypofractionation of radiosurgery in patients with preserved vision before CK treatment results in stable or improved vision.

External application of liver compresses to reduce fatigue in patients with metastatic cancer undergoing radiation therapy, a randomized clinical trial.

BACKGROUND: Liver compresses are frequently used in integrative medicine as supportive therapy during cancer treatment in order to reduce fatigue. We performed a pilot study to test whether the external application of yarrow liver compresses impacts fatigue in patients with metastatic cancer undergoing radiation therapy. METHODS: A randomized prospective pilot trial was performed including patients with brain metastasis or bone metastasis of solid tumors. Patients underwent either palliative radiation therapy (RT) of the metastatic lesions (control group) over two weeks or the same RT with additional external application of yarrow liver compresses once daily during RT. The primary objective was improvement on the general fatigue subscale of the multidimensional fatigue inventory (MFI-20) at the end of treatment, where a mean difference of two points is considered clinically relevant. Secondary objectives included psychological distress, quality of life and qualitative analysis with self-established visual analogue scales (VAS). Mean differences in general fatigue at the end of treatment compared to baseline were analyzed using the ANCOVA test. RESULTS: From 09/2017 to 08/2019 a total of 39 patients were randomized. Due to drop outs 24 patients (12 per group) were available for analysis. Patients in the intervention group received a mean number of 10.5 (range, 7-14) applications of yarrow liver compresses. The mean improvement at the end of therapy on the general fatigue subscale of the MFI-20 was 2 points in favor of the intervention group (p = 0.13), and all other MFI-20 subscales showed at least a trend towards improvement in favor of the intervention group. Likewise, psychological distress and VAS data was improved, the latter reaching statistical significance for the symptoms fatigue, tension and lack of drive. Major toxicities were not observed. CONCLUSIONS: External application of liver compresses appears to reduce fatigue within a clinical relevant range in patients with metastatic cancer undergoing radiation therapy. TRIAL REGISTRATION: ISRCTN, ICTRP DRKS00012999.