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.

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.

Long-term results of robotic radiosurgery for non brachytherapy patients with cervical cancer.

BACKGROUND: Consolidation brachytherapy is a critical treatment component for cervical cancer patients undergoing primary chemoradiation. Some patients are unsuitable for brachytherapy for a variety of reasons. The use of alternatives (LINAC-based stereotactic radiosurgery or external beam boosts) compromise oncologic results in cervical cancer patients. Thus, we evaluated the value of brachytherapy-like doses prescriptions using robotic radiosurgery (CyberKnife®, CR, Acuuray, Sunnyvale, CA, USA). METHODS: From 06/2011 to 06/2015, 31 patients (median age 53 years; range 30-77 years) with histologically proven FIGO stages IB-IVB cervical cancer underwent primary chemoradiation. All patients were either not suitable for intracervical brachytherapy for a variety of reasons or refused the brachytherapy. To achieve an adequate dose within the tumor, a CK boost was applied after fiducial implantation. In 29 patients, a dose of either five times 6 Gy or five times 5 Gy was prescribed to the target volume. Two patients received three times 5 Gy. The target dose was prescribed to the 70% isodose. Treatment toxicity was documented once weekly regarding vaginal mucositis, bladder, and bowel irritation according to CTCAE v. 4.03. If possible 3 months after completion of treatment intracervical curettage was performed to exclude residual tumor and the patients were followed up clinically. Sparing of organs at risk (OAR) and outcome in terms of local control (LC), overall survival (OS), and progression-free survival (PFS) were assessed. RESULTS: Of the 31 patients, 30 have completed CK boost therapy. The median follow-up time was 40 months (range 5-84 months). General treatment tolerability was good. Except for 1 patient, who had diarrhea grade 3, no treatment related side effects above grade 2 were reported. Sparing of OAR was excellent. The 1­, 3­, and 5­year OS rates were 89, 60, and 57% respectively across all stages. Seven patients showed progression (28%), only two of them with local relapse (8%), resulting in an LC rate of 92% after 3 and 5 years. Mean PFS was 41 months (range 2-84 months). Patients with local recurrence had PFS of 5 and 8 months. Five patients developed distant metastases. Fifteen patients (48%) underwent intracervical curettage 3 months after completion of treatment of which 14 (93%) had complete pathologic response. CONCLUSION: Brachytherapy remains the standard of care for patients diagnosed with cervical cancer and indication for primary chemoradiation. In terms of local control, CyberKnife®-based boost concepts provide excellent local control. It can be an alternative for patients who cannot receive adequate brachytherapy. Distant relapse still remains a challenge in this context.

Influence of implant-specific radiation doses on peri-implant hard and soft tissue: An observational pilot study.

OBJECTIVES: The aim of this study was to investigate the influence of real implant-bed-specific radiation doses on peri-implant tissue health in head and neck cancer (HNC) patients after radiotherapy. MATERIAL AND METHODS: Specific radiation doses in the area of 81 implants, in 15 irradiated HNC patients, were analyzed by matching data from the radiotherapy planning system with those of three-dimensional follow-up scans after implantation. Peri-implant bone resorption was measured radiographically after 1 and 3 years, and peri-implant tissue health was evaluated clinically. Individual parameters, such as age, gender, and localization, regarding the implant-specific radiation dose distribution were analyzed statistically. RESULTS: The mean implant-bed-specific radiation dose was high, with 45.95 Gy to the mandible and 29.02 Gy to the maxilla, but significantly lower than the mean total dose to the tumor bed. Peri-implant bone resorption correlated with local inflammation and plaque. After 1 year, women temporarily showed significantly more bone loss than men and implant-specific radiation dose had a significant impact on peri-implant bone loss after 3 years. CONCLUSIONS: The presented method is a feasible option to define precise implant-bed-specific radiation doses for research or treatment planning purposes. Implant-based dental restoration after radiotherapy is a relatively safe procedure, but a negative radiation dose-dependent long-term effect on peri-implant bone resorption calls for interdisciplinary cooperation between surgeons and radio-oncologists to define high-risk areas.

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients.

PURPOSE: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. METHODS: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). RESULTS: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age ≤ 60 years, HIV-PCR ≤ 50 copies, CD4 cells ≤ 200/mm3, cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. CONCLUSIONS: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high.

Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).

BACKGROUND: For loco-regionally advanced, but transorally resectable oropharyngeal cancer (OPSCC), the current standard of care includes surgical resection and risk-adapted adjuvant (chemo) radiotherapy, or definite chemoradiation with or without salvage surgery. While transoral surgery for OPSCC has increased over the last decade for example in the United States due to transoral robotic surgery, this treatment approach has a long history in Germany. In contrast to Anglo-Saxon countries, transoral surgical approaches have been used frequently in Germany to treat patients with oro-, hypopharyngeal and laryngeal cancer. Transoral laser microsurgery (TLM) has had a long tradition since its introduction in the early 70s. To date, the different therapeutic approaches to transorally resectable OPSCC have not been directly compared to each other in a randomized trial concerning disease control and survival. The goal of this study is to compare initial transoral surgery to definitive chemoradiation for resectable OPSCC, especially with regards to local and regional control. METHODS: TopROC is a prospective, two-arm, open label, multicenter, randomized, and controlled comparative effectiveness study. Eligible patients are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 UICC vers. 7) which are amenable to transoral resection. Two hundred eighty patients will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be performed according to daily routine practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant therapy. Patients treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits for 3 years are planned. Primary endpoint is time to local or locoregional failure (LRF). Secondary endpoints include overall and disease free survival, toxicity, and patient reported outcomes. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a scientific support program. DISCUSSION: This study will shed light on an urgently-needed randomized comparison of the strategy of primary chemoradiation vs. primary surgical approach. As a comparative effectiveness trial, it is designed to provide data based on two established regimens in daily clinical routine. TRIAL REGISTRATION: NCT03691441 Registered 1 October 2018 - Retrospectively registered.

Radiosurgery and fractionated stereotactic body radiotherapy for patients with lung oligometastases.

BACKGROUND: Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimens. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT (fSBRT) in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes. METHODS: Fifty-two patients with 94 LM treated with SFRS or fSBRT between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS) and progression-free survival. RESULTS: Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1-5). The median planning target volume (PTV)-encompassing dose for SFRS was 24 Gy (range: 17-26) compared to 45 Gy (range: 20-60) in 2-12 fractions with fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89 and 83% vs. 75 and 59%, respectively (p = 0.026). LM treated with SFSR were significantly smaller (p = 0.001). The 1 and 2-year OS rates for all patients were 84 and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED < 100 Gy were significantly associated with better LC. However, none of these parameters remained significant in the multivariate Cox regression model. OS was significantly better in patients with negative lymph nodes (N0), Karnofsky performance status (KPS) > 70% and time to first metastasis ≥12 months. There was no grade 3 acute or late toxicity. CONCLUSIONS: Longer time to first metastasis, good KPS and N0 predicted better OS. Good LC and low toxicity rates were achieved after short SBRT schedules.

Outcomes and relapse patterns of stage IB grade 2 or 3 endometrial cancer treated with adjuvant vaginal brachytherapy.

INTRODUCTION: Risk factors for pelvic recurrence in early stage endometrial cancer are poorly understood. We sought to describe outcomes, patterns of failure, and risk factors for recurrence among patients with grade 2-3 endometrial cancer with deep myometrial invasion who were treated with vaginal brachytherapy as sole adjuvant therapy after hysterectomy and lymph node dissection. METHODS: We retrospectively reviewed the records of stage I patients with grade 2-3 endometrioid histology and ≥50% myometrial invasion treated at an academic institution from January 2005 to December 2017. Only patients with endometrioid histology were included. Mixed histologies, including papillary serous or clear cell components, were excluded. Further exclusion criteria were International Federation of Gynecology and Obstetrics stage IB grade 1 patients, follow-up time less than 3 months, receipt of pelvic irradiation or any form of systemic therapy (chemotherapy, aromatase inhibitor). Overall survival, disease-free survival, and pelvic recurrence-free survival were calculated with Kaplan-Meier methods. Multivariable Cox proportional hazards regression was used to analyze factors associated with overall survival and disease-free survival. RESULTS: Among 131 consecutive patients identified, 111 (85%) patients met the inclusion criteria. The majority (98.2%) underwent lymph node dissection with ≥10 lymph nodes removed in 78.9%. With a median follow-up of 36 months (IQR 12-70 months), the 3-year overall survival, disease-free survival, and pelvic recurrence-free survival were 89.6%, 90.1%, and 92.8%, respectively. Histologic grade 3, older age, and lymphovascular invasion were not associated with inferior outcomes; however, lower uterine segment involvement (p=0.031), tumor size >4 cm (p=0.024), and <10 lymph nodes removed (p=0.032) were associated with reduced disease-free survival on multivariable analysis. Pelvic recurrence occurred in 12 (11%) patients, most often in the setting of synchronous distant disease (n=9), and was significantly more likely with lower uterine segment involvement. CONCLUSION: Among patients with stage IB grade 2-3 endometrial cancer treated with vaginal brachytherapy, the risk factors for recurrence (larger tumor size and lower uterine segment involvement) in conjunction with established risk factors (high grade, ≥50% myometrial invasion, and lymphovascular invasion) may identify a group of high-risk patients who might benefit from pelvic radiotherapy.

Impact of bladder volume on acute genitourinary toxicity in intensity modulated radiotherapy for localized and locally advanced prostate cancer.

BACKGROUND AND PURPOSE: To evaluate the effect of changes in bladder volume during high-dose intensity-modulated-radiotherapy (IMRT) of prostate cancer on acute genitourinary (GU) toxicity and prospectively evaluate a simple biofeedback technique for reproducible bladder filling with the aim of reducing acute GU toxicity. METHODS: One hundred ninety-three patients were trained via a biofeedback mechanism to maintain a partially filled bladder with a reproducible volume of 200-300 cc at planning CT and subsequently at each fraction of radiotherapy. We prospectively analyzed whether and to what extent the patients' ability to maintain a certain bladder filling influenced the degree of acute GU toxicity and whether cut-off values could be differentiated. RESULTS: We demonstrated that the ability to reach a reproducible bladder volume above a threshold volume of 180 cc and maintain that volume via biofeedback throughout treatment predicts for a decrease in acute GU toxicity during curative high-dose IMRT of the prostate. Patients who were not able to reach a partial bladder filling to that cut-off value and were not able to maintain a partially filled bladder throughout treatment had a significantly higher risk of developing ≥grade 2 GU acute toxicity. CONCLUSION: Our results support the hypothesis that a biofeedback training for the patient is an easy-to-apply, useful, and cost-effective tool for reducing acute GU toxicity in high-dose IMRT of the prostate. Patients who are not able to reach and maintain a certain bladder volume during planning and treatment-two independent risk factors-might need special consideration.

Unilateral and bilateral neck SIB for head and neck cancer patients : Intensity-modulated proton therapy, tomotherapy, and RapidArc.

AIM: To compare simultaneous integrated boost plans for intensity-modulated proton therapy (IMPT), helical tomotherapy (HT), and RapidArc therapy (RA) for patients with head and neck cancer. PATIENTS AND METHODS: A total of 20 patients with squamous cell carcinoma of the head and neck received definitive chemoradiation with bilateral (n = 14) or unilateral (n = 6) neck irradiation and were planned using IMPT, HT, and RA with 54.4, 60.8, and 70.4 GyE/Gy in 32 fractions. Dose distributions, coverage, conformity, homogeneity to planning target volumes (PTV)s and sparing of organs at risk and normal tissue were compared. RESULTS: All unilateral and bilateral plans showed excellent PTV coverage and acceptable dose conformity. For unilateral treatment, IMPT delivered substantially lower mean doses to contralateral salivary glands (< 0.001-1.1 Gy) than both rotational techniques did (parotid gland: 6-10 Gy; submandibular gland: 15-20 Gy). Regarding the sparing of classical organs at risk for bilateral treatment, IMPT and HT were similarly excellent and RA was satisfactory. CONCLUSION: For unilateral neck irradiation, IMPT may minimize the dry mouth risk in this subgroup but showed no advantage over HT for bilateral neck treatment regarding classical organ-at-risk sparing. All methods satisfied modern standards regarding toxicity and excellent target coverage for unilateral and bilateral treatment of head and neck cancer at the planning level.

Comparative treatment planning study on sequential vs. simultaneous integrated boost in head and neck cancer patients: Differences in dose distributions and potential implications for clinical practice.

AIM: The purpose of this work was to compare sequential (SeqB) versus simultaneous integrated boost (SIB) radiotherapy plans delivered with volumetric modulated arc therapy (VMAT) for patients with locally advanced squamous cell cancer of the head and neck (HNSCC). PATIENTS AND METHODS: SeqB and SIB plans using VMAT for 10 HNSCC patients given definitive chemoradiation were generated and analysed for differences in dose distribution, coverage, conformity and homogeneity to the planning target volumes (PTV) 1-3 and sparing of organs at risk (OAR). RESULTS: The mean delineated volumes ± standard deviations were 137.7 ± 44.8, 351.3 ± 83.9 and 895.6 ± 120.5 cm3 for PTV1-3. The mean volumes encompassed by the corresponding 95 % isodoses were 281 (+ 110 %) ± 73.4, 712.2 (+ 115 %) ± 146.4 and 1381.1 (+ 54 %) ± 217.3 cm3 with SeqB and 138.2 (+ 7 %) ± 40.1, 380.4 (+ 11 %) ± 91.9 and 1057.3 (+ 21 %) ± 161.4 cm3 with SIB for PTV1-3, respectively. Both strategies achieved excellent PTV coverage. SeqB provided significantly better coverage of PTV1 and 3, worse conformity for PTV1-3 and a higher mean dose than prescribed (111-115 %) to PTV2 and 3 (p ≤ 0.007). Both strategies provided satisfactory OAR sparing. CONCLUSION: This study showed significant dosimetric differences with potential clinical relevance between two VMAT boost strategies regarding coverage, conformity and dose to the PTVs. SIB might cause less toxicity. A clinical phase III/IV trial endorsed by the German Head and Neck Clinical Trials Group (IAG-KHT) will evaluate differences in acute/late toxicity as well as in locoregional recurrences between the two boost techniques.

Haemoglobin and creatinine values as prognostic factors for outcome of concurrent radiochemotherapy in locally advanced head and neck cancers : Secondary results of two European randomized phase III trials (ARO 95-06, SAKK 10/94).

BACKGROUND: To determine the influence of baseline laboratory values on treatment outcome in patients with locally advanced head and neck cancer (HNSCC). METHODS: Data of the randomized trials ARO 95 -06 (n = 384) and SAKK 10 /94 (n = 224) were pooled for a total sample size of 608 patients. Haemoglobin (Hb) and creatinine (Cr) were available at baseline and their association with locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) was analyzed using univariable and multivariable Cox regression models. RESULTS: A total of 580 and 564 patients were available with baseline Hb and Cr values in the pooled analysis. Univariable analyses revealed that lower baseline Hb values were significantly associated with decreased LRRFS, DMFS, CSS and OS. This effect remained significant for OS when the treatment arms (radiotherapy [RT] alone vs. chemoradiation [CRT]) were analyzed separately. Higher baseline Cr was associated with improved OS in the pooled analysis. Interestingly, the prognostic value of baseline Cr appeared to be limited to the subgroup of 284 patients who were treated with CRT. In the multivariable Cox regression model lower baseline Hb remained associated with decreased OS both in the patients who received CRT (HR 0.79, 95 % CI 0.66-0.94, p = 0.009) and in those patients who underwent RT alone (HR 0.67, 95 % CI 0.58-0.78, p < 0.001). Increased baseline Cr remained significantly associated with improved OS in patients who underwent CRT (HR 0.79, 95 % CI 0.69-0.92, p = 0.002) but not in those patients who underwent RT alone. CONCLUSIONS: An association between lower baseline Hb and inferior treatment outcome was confirmed. Baseline Cr was introduced as a prognosticator of outcome after CRT for locally advanced HNSCC.

Changes in Peri-Implant Bone Level and Effect of Potential Influential Factors on Dental Implants in Irradiated and Nonirradiated Patients Following Multimodal Therapy Due to Head and Neck Cancer: A Retrospective Study.

PURPOSE: The aim of the present study was to evaluate changes in the marginal bone level of dental implants in irradiated and nonirradiated patients and to identify possible influential factors. MATERIALS AND METHODS: Thirty-six patients with 194 implants were involved in the study (7 women and 29 men). The mean age of the patients was 65.8 years (39 to 90 yr). In all patients, a squamous cell carcinoma in the floor of the mouth involving the mandible or tongue was surgically removed. In 17 patients, adjuvant radiochemotherapy was completed a minimum of 6 months before implant placement. Mean crestal bone changes using standardized orthopantomographs were evaluated. The Spearman rank-order correlation coefficient and Mann-Whitney U test were used to determine correlations between bone crestal changes and age, gender, radiation therapy (yes vs no), augmentation (yes vs no), and type of superstructure. RESULTS: In total, 194 implants were placed (73 in the maxilla and 121 in the mandible). Mean amounts of peri-implant bone loss were 1 mm mesially and 0.9 mm distally after 1 year and 1.4 mm mesially and 1.3 mm distally after 3 years. During the observation period, 4 implants were lost. The overall success rate was 98.4% (maxilla, 100%; mandible, 96.7%). There was no relevant difference in changes in bone level according to age, gender, prosthetic superstructure, or augmentation procedure (yes vs no). Radiation therapy was found to have an effect on crestal bone loss. CONCLUSION: The present study showed a high success rate of dental implants after 3 years. Peri-implant crestal bone loss was comparable to that in patients without tumor. The mean amount of crestal bone change in irradiated patients was twice as high as that in nonirradiated patients.

Nodal yield of neck dissections and influence on outcome in laryngectomized patients.

The appropriate extent of neck dissection (ND) in head and neck squamous cell carcinoma (SCC) continues to be investigated. This study aimed to determine whether the extent of ND as measured by nodal yield (NY) is a prognostic factor in patients undergoing primary total laryngectomy (TL) for advanced laryngeal SCC. A retrospective review at a tertiary referral centre identified 54 patients who underwent TL with elective (n = 39, cN0) or therapeutic (n = 15, cN+) ND with curative intent between 2002 and 2014. Survival analysis was obtained via regression analysis, calculated for overall (OS) and disease-free survival (DFS). Stage-independent 5-year OS was 32.1 %. Mean NY was 18.67 (standard deviation 9.898; range 0-45). The rate of cervical lymph node metastasis on pathology (pN+) was 27.8 %. Uni- and multivariate regression analysis detected no association between NY and OS or DFS (P ≥ 0.05). Advantages in OS and DFS were seen among patients without cervical lymph node metastasis (pN0) in comparison to those with pN+ necks (OS: hazard ratio [HR] 0.179; 95 % confidence interval [CI] 0.046-0.693; P = 0.013, and DFS: HR 0.190; 95 % CI 0.061-0.590; P = 0.004). ND resulted in pathologic upstaging of the neck in seven patients and downgrading in eight; increasing NY was not associated with an increased probability of a change in nodal stage. No significant association was found between NY and OS or DFS in patients undergoing TL with ND as primary therapy for advanced laryngeal SCC.

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.

De-intensification of postoperative radiotherapy in head and neck cancer irrespective of human papillomavirus status-results of a prospective multicenter phase II trial (DIREKHT Trial).

Background: Current standard treatment concepts in head and neck squamous cell carcinoma (HNSCC) are based on former studies using 2D and 3D treatment plans. However, modern radiation techniques allow for a more precise and individual dose application. Therefore, in a clearly defined patient population, de-intensified risk-adapted radiation is investigated. Methods: Patients with newly diagnosed HNSCC after surgery (with resection margins ≥1 mm and cM0) with the following tumor stages (TNM 7th Edition) were eligible for the study: oral cavity, oropharynx, or larynx: pT1-3, pN0-pN2b; hypopharynx: pT1-2, pN1. The patients should have either a low risk of local recurrence [≤pT2, resection margin ≥5 mm, no peritumoral lymphangiosis (L0), and no perineural invasion] or contralateral lymph node metastasis (≤3 ipsilateral lymph node metastases, in case of well-lateralized oropharyngeal or oral cavity cancer contralateral cN0, otherwise pN0). Patients were assigned to three different treatment regimes with reduction of the treated volume, radiation dose, or both, according to tumor stage and results of surgery performed. The primary objective was to show an LRR of <10% after 2 years. Findings: A total of 150 patients were enrolled. Tumor localizations were as follows: n = 53 (35.3%), oral cavity; n = 94 (62.7%), oropharynx (82% HPV-positive); n = 2 (1.3%), hypopharynx; and n = 1 (0.7%), larynx. A total of 61 patients (41.0%) were stage IVA, 81 (54.0%) were stage III, and 8 (5.3%) were stage II. Median follow-up was 36 months. Cumulative incidence of 2y-LRR was 5.6% (95% CI: 1.7%-9.2%) in the whole study population and 14.1% (95% CI: 3.8%-23.2%) in patients with oral cavity cancer. Cumulative incidence of 2y-LRR in non-irradiated or dose-reduced regions was 3.5% (95% CI: 0.4%-6.5%). After 2 years, disease-free survival was 92% (95% CI: 87%-96%) and overall survival was 94% (95% CI: 90%-98%) for the complete study cohort. Acute III° toxicity was as follows: dysphagia, 30%; xerostomia, 7%; mucositis, 19%; and dermatitis, 4%. Dysphagia and xerostomia decrease over time. After 27 months, late dysphagia III° and xerostomia II° were 1% and 9%, respectively. Interpretation: The study met its primary objective. De-intensification of postoperative radiotherapy irrespective of HPV status in a predefined patient population is associated with a favorable toxicity profile without compromising LRR. In an unplanned subgroup analysis, a significantly increased risk of LRR was observed in patients with oral cavity cancer. In these patients, de-intensified radiotherapy should be applied with caution.

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.

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.

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.

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.