Immunotherapy in elderly head and neck cancer patients: a systematic review and meta-analysis.

Introduction: Over the past years, there has been a growing interest in the role of immunotherapy in locally advanced (LA) and recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). High-quality data from prospective trials are lacking for the elderly subpopulation. This systematic review and meta-analysis aims to review the efficacy and safety of immunotherapy in older patients. Methods: A systematic literature search was conducted. Randomized clinical trials providing outcome data on a subgroup of elderly (>65 years old) were available for meta-analysis. Primary outcomes of interest were OS and PFS for efficacy analysis. Results: Seven studies were included in the systematic review and four in the efficacy analysis. The pooled analysis of OS and PFS showed a consistent benefit (HR 0.78 and 0.91, respectively). Conclusions: Immunotherapy may be an effective and well-tolerated treatment option in the elderly population, but more prospective and randomized data are needed. Systematic Review Registration: PROSPERO (CRD42022333891).

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial.

BACKGROUND: Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. METHODS: In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. DISCUSSION: To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506.

Postoperative radiotherapy for meningiomas - a decision-making analysis.

BACKGROUND: The management of meningiomas is challenging, and the role of postoperative radiotherapy is not standardized. METHODS: Radiation oncology experts in Swiss centres were asked to participate in this decision-making analysis on the use of postoperative radiotherapy (RT) for meningiomas. Experts from ten Swiss centres agreed to participate and provided their treatment algorithms. Their input was converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies in clinical routine. RESULTS: Several criteria used for decision-making in postoperative RT in meningiomas were identified: histological grading, resection status, recurrence, location of the tumour, zugzwang (therapeutic need to treat and/or severity of symptoms), size, and cell division rate. Postoperative RT is recommended by all experts for WHO grade III tumours as well as for incompletely resected WHO grade II tumours. While most centres do not recommend adjuvant irradiation for WHO grade I meningiomas, some offer this treatment in recurrent situations or routinely for symptomatic tumours in critical locations. The recommendations for postoperative RT for recurrent or incompletely resected WHO grade I and II meningiomas were surprisingly heterogeneous. CONCLUSIONS: Due to limited evidence on the utility of postoperative RT for meningiomas, treatment strategies vary considerably among clinical experts depending on the clinical setting, even in a small country like Switzerland. Clear majorities were identified for postoperative RT in WHO grade III meningiomas and against RT for hemispheric grade I meningiomas outside critical locations. The limited data and variations in clinical recommendations are in contrast with the high prevalence of meningiomas, especially in elderly individuals.

Stage III N2 non-small cell lung cancer treatment: decision-making among surgeons and radiation oncologists.

BACKGROUND: Stage III N2 non-small cell lung cancer (NSCLC) is a very heterogeneous disease associated with a poor prognosis. A number of therapeutic options are available for patients with Stage III N2 NSCLC, including surgery [with neoadjuvant or adjuvant chemotherapy (CTx)/neoadjuvant chemoradiotherapy (CRT)] or CRT potentially followed by adjuvant immunotherapy. We have no clear evidence demonstrating a significant survival benefit for either of these approaches, the selection between treatments is not always straightforward and can come down to physician and patient preference. The very heterogeneous definition of resectability of N2 disease makes the decision-making process even more complex. METHODS: We evaluated the treatment strategies for preoperatively diagnosed stage III cN2 NSCLC among Swiss thoracic surgeons and radiation oncologists. Treatment strategies were converted into decision trees and analysed for consensus and discrepancies. We analysed factors relevant to decision-making within these recommendations. RESULTS: For resectable "non-bulky" mediastinal lymph node involvement, there was a trend towards surgery. Numerous participants recommend a surgical approach outside existing guidelines as long as the disease was resectable, even in multilevel N2. With increasing extent of mediastinal nodal disease, multimodal treatment based on radiotherapy was more common. CONCLUSIONS: Both, surgery- or radiotherapy-based treatment regimens are feasible options in the management of Stage III N2 NSCLC. The different opinions reflected in the results of this manuscript reinforce the importance of a multidisciplinary setting and the importance of shared decision-making with the patient.

Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study.

BACKGROUND: The CATNON trial investigated the addition of concurrent, adjuvant, and both current and adjuvant temozolomide to radiotherapy in adults with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas. The benefit of concurrent temozolomide chemotherapy and relevance of mutations in the IDH1 and IDH2 genes remain unclear. METHODS: This randomised, open-label, phase 3 study done in 137 institutions across Australia, Europe, and North America included patients aged 18 years or older with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas and a WHO performance status of 0-2. Patients were randomly assigned (1:1:1:1) centrally using a minimisation technique to radiotherapy alone (59·4 Gy in 33 fractions; three-dimensional conformal radiotherapy or intensity-modulated radiotherapy), radiotherapy with concurrent oral temozolomide (75 mg/m2 per day), radiotherapy with adjuvant oral temozolomide (12 4-week cycles of 150-200 mg/m2 temozolomide given on days 1-5), or radiotherapy with both concurrent and adjuvant temozolomide. Patients were stratified by institution, WHO performance status score, age, 1p loss of heterozygosity, the presence of oligodendroglial elements on microscopy, and MGMT promoter methylation status. The primary endpoint was overall survival adjusted by stratification factors at randomisation in the intention-to-treat population. A second interim analysis requested by the independent data monitoring committee was planned when two-thirds of total required events were observed to test superiority or futility of concurrent temozolomide. This study is registered with ClinicalTrials.gov, NCT00626990. FINDINGS: Between Dec 4, 2007, and Sept 11, 2015, 751 patients were randomly assigned (189 to radiotherapy alone, 188 to radiotherapy with concurrent temozolomide, 186 to radiotherapy and adjuvant temozolomide, and 188 to radiotherapy with concurrent and adjuvant temozolomide). Median follow-up was 55·7 months (IQR 41·0-77·3). The second interim analysis declared futility of concurrent temozolomide (median overall survival was 66·9 months [95% CI 45·7-82·3] with concurrent temozolomide vs 60·4 months [45·7-71·5] without concurrent temozolomide; hazard ratio [HR] 0·97 [99·1% CI 0·73-1·28], p=0·76). By contrast, adjuvant temozolomide improved overall survival compared with no adjuvant temozolomide (median overall survival 82·3 months [95% CI 67·2-116·6] vs 46·9 months [37·9-56·9]; HR 0·64 [95% CI 0·52-0·79], p<0·0001). The most frequent grade 3 and 4 toxicities were haematological, occurring in no patients in the radiotherapy only group, 16 (9%) of 185 patients in the concurrent temozolomide group, and 55 (15%) of 368 patients in both groups with adjuvant temozolomide. No treatment-related deaths were reported. INTERPRETATION: Adjuvant temozolomide chemotherapy, but not concurrent temozolomide chemotherapy, was associated with a survival benefit in patients with 1p/19q non-co-deleted anaplastic glioma. Clinical benefit was dependent on IDH1 and IDH2 mutational status. FUNDING: Merck Sharpe & Dohme.

Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations.

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1R132H mutations. Patients harbouring IDH1R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1R132H have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1R132H mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication.

MRI and 18FET-PET Predict Survival Benefit from Bevacizumab Plus Radiotherapy in Patients with Isocitrate Dehydrogenase Wild-type Glioblastoma: Results from the Randomized ARTE Trial.

PURPOSE: To explore a prognostic or predictive role of MRI and O-(2-18F-fluoroethyl)-L-tyrosine (18FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma. PATIENTS AND METHODS: Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm. RESULTS: Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm3 0.94; 95% confidence interval (CI), 0.89-0.99] and for higher ADC (HR 0.18; CI, 0.05-0.66). Higher 18FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only (P = 0.09). High 18FET-TBR of noncontrast-enhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16-30.8). CONCLUSIONS: Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent 18FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome.

Localized Non-melanoma Skin Cancer: Risk Factors of Post-surgical Relapse and Role of Postoperative Radiotherapy.

OPINION STATEMENT: The mainstay treatment of localized non-melanoma skin cancer (NMSC) is surgical excision or Mohs surgery. However, approximately 5% of patients with NMSC harbor high-risk clinicopathologic features for loco-regional recurrence, and distant metastasis. Prognostic factors such as close or positive margins, tumor size ≥ 2 cm, poor tumor differentiation, perineural invasion, depth of invasion, and immunosuppression have all been associated with increased loco-regional recurrence and impaired survival rates. In these patients more aggressive treatments are needed and radiotherapy (RT) is often discussed as adjuvant therapy after surgical resection. Due to the retrospective setting and the heterogeneity of the available studies, indications for adjuvant RT in patients with localized resected NMSC harboring high-risk features remain debated. Studies highlighting the limitations of our current understanding of the independent prognosis of each risk factor are needed to better define the role of adjuvant RT on outcome of localized NMSC and standardize its indications in the clinical setting.

Impact of Early Prophylactic Cranial Irradiation With Hippocampal Avoidance on Neurocognitive Function in Patients With Limited Disease Small Cell Lung Cancer. A Multicenter Phase 2 Trial (SAKK 15/12).

PURPOSE: Our purpose was to evaluate neurocognitive function (NCF) and clinical outcomes after early hippocampal avoidance (HA) prophylactic cranial irradiation (PCI) in limited disease (LD) small cell lung cancer (SCLC). METHODS AND MATERIALS: In a phase 2 trial, patients with LD SCLC received HA-PCI concomitant with the second cycle of chemotherapy and thoracic radiation therapy. All patients underwent objective NCF testing at baseline, 6 weeks, and 6 and 12 months after HA-PCI. NCF tests included Hopkins Verbal Learning Test Revised, Controlled Oral Word Association, and Trail Making Tests A and B. The primary endpoint was NCF decline at 6 months after HA-PCI. We assumed ≤30% of patients with no NCF decline to be unpromising. Secondary endpoints included brain metastases-free survival (BMFS), overall survival (OS), and safety of the concomitant treatment. RESULTS: Among the 44 patients enrolled in the trial, 38 had evaluable NCF assessment at 6 months after HA-PCI. The proportion of evaluable patients showing no NCF decline at 6 and 12 months was 34.2% (90% confidence interval [CI], 21.6-48.8) and 48.5% (95% CI, 30.8-66.5), respectively. Median follow-up was 13.2 months (95% CI, 12.6-14.1). At 12 months, BMFS was 84.2% and OS was 87.7% (95% CI, 73.0-94.7). Four patients died of SCLC, 1 of respiratory failure, 1 of hemorrhage, and 1 for unknown reason. The most frequently reported grade ≥3 acute adverse events were anemia (21.4%), febrile neutropenia (19.1%), and fatigue (14.3%). CONCLUSIONS: The proportion of patients showing no NCF decline 6 and 12 months after early HA-PCI does not appear to be better than, but rather similar to, that observed in patients receiving sequential PCI without HA. Early HA-PCI in LD SCLC is feasible, with observation of promising BMFS and OS in this selected population.

Influencing Factors on Radiotherapy Outcome in Stage I-II Glottic Larynx Cancer-A Multicenter Study.

Background and Purpose: Larynx cancer represents one of the most frequently diagnosed head and neck malignancies, which is most often confined to the glottic area. The aim of this study was to report the oncological outcome and identify prognostic factors in early-stage glottic squamous cell carcinoma treated with radiotherapy. Material and Methods: Patients (n = 761) diagnosed and treated in 10 centers between 1990 and 2015 were retrospectively analyzed. Probabilities of loco-regional control (LRC) and overall survival (OS) were calculated and possible prognostic factors were analyzed using Cox proportional hazards models. Results: The median follow-up was 63 months (range: 2-243). Three hundred and sixty-four, 148 and 249 patients had cT1a, cT1b, and cT2 stage I-II disease, respectively. Five and 10-years LRC/OS rates in the whole cohort were 83/82% and 80/68%, respectively. Three patients developed distant recurrences. In univariate analysis, male sex (HR: 3.49; 95% CI: 1.47-11.37; p < 0.01), T2 vs. T1a (HR: 1.62; 95% CI: 1.08-2.43; p = 0.02) and anterior commissure involvement (ACI) (HR: 1.66; 95% CI: 1.38-2.45; p < 0.01) were associated with impaired LRC. In multivariate analysis, male sex (HR: 3.42; 95% CI: 1.44-11.17; p < 0.01) and ACI (HR: 1.51; 95% CI: 1.01-2.28; p = 0.047) remained poor prognostic factors. No relation of treatment technique and biologically equivalent dose (BED) to oncological outcome was identified except for higher BED10(L = 25; T = 1) yielding better LRC in T1a tumors (p = 0.04) in univariate analyses. Conclusion: Our results highlight the negative impact of ACI on tumor control. A less-expected finding was the impact of sex on tumor control. Further research is needed to validate its prognostic value and investigate any related biologic or behavioral factors, which may be modified to improve oncologic outcome.

Neck management in head and neck squamous cell carcinomas: where do we stand?

Head and neck squamous-cell carcinomas (HNSCCs) have a significant lymph node tropism. This varies considerably depending on the primary tumor site and the Human Papillomavirus (HPV) status of the disease. The best therapeutic option, between up-front lymph node dissection and chemoradiotherapy (CRT) +/- followed by lymph node dissection in case of persistent lymphadenopathy or regional relapse, remains unclear. The purpose of this review is to discuss the pros and cons related to the different approaches of the neck management in HNSCC. A narrative review of the management of the cervical lymph nodes was undertaken. Searches of PubMed database were performed using the terms 'neck management' OR 'cervical lymphadenopathies' AND 'head and neck neoplasms'. Recent advances in imaging, pathological analysis, surgery and radiotherapy let to personalize the type of lymph node dissection and, the volumes of radiation therapy. Excluding inoperable patients and unresectable diseases, N3 lymphadenopathies, as well as bulky N2 stages, specifically HPV- or necrotic nodes, would be in favor of an up-front surgical approach, while HPV+ diseases, and lymphadenopathies of unknown primary would support CRT first. However, efficacy of such strategies is challenged by a significant morbidity in the medium and long terms. In the absence of higher level of evidence, the decision-making tools for the neck dissection before or after the CRT are based on the Mehanna's trial and retrospective studies with significant biases. Consequently, the approaches and the ensuing outcomes remain not homogenous depending on the centers' experience, in the context of limited data, especially for N2-3 HPV- HNSCC.

Clinical experience with lung-specific electromagnetic transponders for real-time tumor tracking in lung stereotactic body radiotherapy.

BACKGROUND AND PURPOSES: Motion management is crucial for optimal stereotactic body radiotherapy (SBRT) of moving targets. We aimed to describe our clinical experience with real-time tracking of lung-specific electromagnetic transponders (EMTs) for SBRT of early stage non-small cell lung cancer in free-breathing (FB) or deep inspiration breath-hold (DIBH). MATERIAL AND METHODS: Seven patients were implanted with EMTs. Simulation for SBRT was performed in FB and in DIBH. We prescribed 60 Gy in 3, 5 or 8 fractions to the tumor and delivered SBRT with volumetric modulated arcs and a 6 MV flattening filter free photon beam. Patients' setup at the linac was performed using EMT positions and cone-beam CT (CBCT) verification. Four patients were treated in DIBH because of a dosimetric benefit. We analysed patient alignment and treatment delivery parameters using DIBH or FB and EMT real-time tracking. RESULTS: There were no complications from the EMT implantation. Visual inspection of CBCT before and/or after SBRT revealed good alignment of structures and EMTs. The median setup time was 9.8 min (range: 4.6-34.1 min) and the median session time was 14.7 min (range: 7.3-36.5 min). EMT positions in lungs remained stable during overall treatment and allowed real-time tracking both in FB and in DIBH SBRT. The treatment beam was gated when EMT centroid position exceeded tolerance thresholds ensuring correct delivery of radiation to the tumor. CONCLUSION: Using EMTs for real-time tracking of tumor motion during lung SBRT proved to be safe, accurate and easy to integrate clinically for treatments in FB or DIBH.

Utility of MRI with morphologic and diffusion weighted imaging in the detection of post-treatment nodal disease in head and neck squamous cell carcinoma.

PURPOSE: To determine the diagnostic performance of morphologic MRI with diffusion weighted imaging (DWIMRI) for the detection of post-treatment lymph node (LN) recurrence of head and neck squamous cell carcinoma (HNSCC). METHODS: This retrospective study is based on 33 HNSCC patients who underwent DWIMRI with apparent diffusion coefficient (ADC) measurements for suspected post-treatment loco-regional failure. Two radiologists, blinded to clinical/histopathological data, analyzed MR images according to established morphologic criteria and measured ADC values by drawing regions of interest on each normal/abnormal looking lymph node (LN). Histopathological findings in 40 neck dissections, 133 LN-levels and 755 LNs served as gold standard. RESULTS: Malignant LNs had lower ADCmean values than benign LNs (1.15 ±â€¯0.35 × 10-3 mm2/s versus 1.28 ±â€¯0.28 × 10-3 mm2/s, p = .028). The optimal ADCmean threshold to differentiate malignant from benign LNs was 1.1695 × 10-3 mm2/s. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (95%CI in parentheses) of DWIMRI with morphologic criteria and ADCmean <1.1695 × 10-3 mm2/s were: (a) 100%(86.2;100), 44.4%(15.3;77.3), 86.1%(69.7;94.7), and 100%(39.5;100) per neck dissection; (b) 83.6%(69.7;92.2), 91.6%(83.0;96.2), 85.4%(71.6;93.4), and 90.5%(81.7;95.5) per LN-level; (c) 53.1%(43.5;62.4), 95.5%(93.5;96.9), 67.4%(56.6;76.7), and 92.0%(89.6;93.9) per LN, respectively. CONCLUSION: The high NPV of DWIMRI irrespective of analysis type (per neck dissection/per neck level/per lymph node) make it a useful follow-up tool after treatment.

[Sexual health after radiotherapy]. / La santé sexuelle après radiothérapie.

The impact of locoregional toxicity after radiotherapy on sexual function is the objective of this review. We explore those organs affected by cancer that are obviously implied in patients' intimate lives : cancers of the breast, prostate, pelvic region, and ENT region. However, we strongly believe that any patient diagnosed with cancer, and treated for one, could by all means be exposed to psychological and somatic changes leading to deterioration of their sexuality.

L'évaluation de l'impact locorégional après un traitement de radiothérapie sur la fonction sexuelle est l'objectif de cet article. Nous passerons en revue les organes atteints de cancer dont l'implication dans la vie intime des patients nous a semblé la plus parlante : les cancers du sein, de la prostate, de la région pelvienne et de la sphère ORL. Néanmoins, nous sommes convaincus que tout patient avec un diagnostic de cancer, et traité pour celui-ci, peut être exposé à des séquelles psychologiques et somatiques entraînant une baisse de sa sexualité.

Local recurrence of squamous cell carcinoma of the head and neck after radio(chemo)therapy: Diagnostic performance of FDG-PET/MRI with diffusion-weighted sequences.

PURPOSE: To determine the diagnostic performance of FDG-PET/MRI with diffusion-weighted imaging (FDG-PET/DWIMRI) for detection and local staging of head and neck squamous cell carcinoma (HNSCC) after radio(chemo)therapy. MATERIALS AND METHODS: This was a prospective study that included 74 consecutive patients with previous radio(chemo)therapy for HNSCC and in whom tumour recurrence or radiation-induced complications were suspected clinically. The patients underwent hybrid PET/MRI examinations with morphological MRI, DWI and FDG-PET. Experienced readers blinded to clinical/histopathological data evaluated images according to established diagnostic criteria taking into account the complementarity of multiparametric information. The standard of reference was histopathology with whole-organ sections and follow-up ≥24 months. Statistical analysis considered data clustering. RESULTS: The proof of diagnosis was histology in 46/74 (62.2%) patients and follow-up (mean ± SD = 34 ± 8 months) in 28/74 (37.8%). Thirty-eight patients had 43 HNSCCs and 46 patients (10 with and 36 without tumours) had 62 benign lesions/complications. Sensitivity, specificity, and positive and negative predictive value of PET/DWIMRI were 97.4%, 91.7%, 92.5% and 97.1% per patient, and 93.0%, 93.5%, 90.9%, and 95.1% per lesion, respectively. Agreement between imaging-based and pathological T-stage was excellent (kappa = 0.84, p < 0.001). CONCLUSION: FDG-PET/DWIMRI yields excellent results for detection and T-classification of HNSCC after radio(chemo)therapy. KEY POINTS: • FDG-PET/DWIMRI yields excellent results for the detection of post-radio(chemo)therapy HNSCC recurrence. • Prospective one-centre study showed excellent agreement between imaging-based and pathological T-stage. • 97.5% of positive concordant MRI, DWI and FDG-PET results correspond to recurrence. • 87% of discordant MRI, DWI and FDG-PET results correspond to benign lesions. • Multiparametric FDG-PET/DWIMRI facilitates planning of salvage surgery in the irradiated neck.

Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy.

BACKGROUND: Osteoradionecrosis (ORN) of the mandible is a late toxicity affecting patients treated with radiotherapy for head and neck malignancies. To the authors' knowledge, ORN has no standardized grading system and its reporting is based on retrospective findings in heterogeneous patient populations. The rate of ORN in the era of intensity-modulated radiotherapy (IMRT) still is unknown. METHODS: The authors report the incidence of ORN from prospectively collected data regarding 1196 patients who were diagnosed with squamous cell carcinoma of the oropharynx and treated with curative-intent IMRT, with or without concomitant systemic treatment, from January 2005 to December 2014. Each case of ORN was graded according to its severity. Clinical and dosimetric comparisons were performed between patients with ORN and a matched control cohort of patients without ORN. RESULTS: The actuarial rate of ORN of the mandible was 3% at 1 year, 5% at 3 years, and 7% at 5 years. On multivariable analysis, smoking (hazard ratio, 1.9; 95% confidence interval, 1.07-3.4 [P = .03]) and T classification (hazard ratio, 1.78; 95% confidence interval, 1.02-3.1 [P = .041]) were found to be statistically significant risk factors. The presence of cardiovascular comorbidities, use of bisphosphonates, and pre-IMRT dental extractions were found to be different between the matched cohorts. The mandibular volume receiving 50 grays (Gy) (in cm3 ) and the volume receiving 60 Gy (in cm3 ) were found to be associated with ORN on multivariable analysis in the matched cohort patients receiving an IMRT regimen of 2 Gy per fraction. CONCLUSIONS: ORN is relatively uncommon among patients with oropharyngeal carcinoma who are treated with IMRT, but continues to occur beyond 5 years after treatment. Modifiable risk factors that are associated with higher rates of ORN include smoking and the use of bisphosphonates. Minimizing the volumes of the mandible receiving >50 Gy or > 60 Gy also may have an effect on the ORN rate. Cancer 2017;123:3691-3700. © 2017 American Cancer Society.

Exploring the Impact of Human Papillomavirus Status, Comorbidity, Polypharmacy, and Treatment Intensity on Outcome of Elderly Oropharyngeal Cancer Patients Treated With Radiation Therapy With or Without Chemotherapy.

PURPOSE: To explore the impact of tumor human papillomavirus (HPV) status, comorbidity, polypharmacy, and treatment intensity on overall survival (OS) of elderly oropharyngeal cancer (OPC) patients. METHODS AND MATERIALS: All elderly (>70 years) OPC patients receiving definitive (chemo-) radiation therapy in 2000 to 2013 were reviewed. Charlson comorbidity index (CCI, comorbidity alone) and the comorbidity-polypharmacy score (CPS, comorbidity and medication) were calculated. Overall survival was compared between HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Multivariable analyses (MVA) incorporating either the CCI (MVA-CCI) or the CPS (MVA-CPS) identified survival predictors. RESULTS: Among 231 of 287 patients (80%) with p16 staining, 117 were HPV+ and 114 HPV-. Systemic treatments were administered in 48 patients (21%) (chemotherapy 17; epidermal growth factor receptor inhibitor 31). The distribution of CCI (P=.59), CPS (P=.23), and age (P=.50) were similar between HPV+ versus HPV- cohorts. Median follow-up was 4.3 years. The HPV+ patients had better 5-year OS (57% vs 32%, P<.001) versus HPV- patients. Multivariable analysis adjusted for T-/N-category confirmed that HPV+ status (MVA-CCI: hazard ratio [HR] 0.58, P=.01; MVA-CPS: HR 0.60, P=.02), Zubrod scale score (0-1) (MVA-CCI: HR 0.44, P<.001; MVA-CPS: HR 0.43, P<.001), and higher radiation therapy dose (MVA-CCI: HR 0.97, P=.001; MVA-CPS: HR 0.96, P<.001) were correlated with higher OS. A marginal inverse correlation between CPS and OS was observed in the entire cohort (HR 1.05, P=.05) and was stronger for the HPV+ cohort (HR 1.11, P=.02). Nonsignificant higher OS was also found with ≤20 pack-years of smoking (MVA-CCI: P=.10; MVA-CPS: P=.15) and with systemic treatments (MVA-CCI: P=.13; MVA-CPS: P=.19). No association with OS was found for CCI (P=.46). CONCLUSION: Elderly HPV+ OPC patients have longer survival than their HPV- counterparts. Lower Zubrod scale score and higher radiation therapy dose are associated with longer OS, whereas fewer smoking pack-years and systemic agents have nonsignificant associations. Comorbidity-polypharmacy score, but not CCI, is correlated with OS, especially in HPV+ patients, suggesting the potential importance of assessing polypharmacy in addition to comorbidity burden in this population.

Results of Dose-adapted Salvage Radiotherapy After Radical Prostatectomy Based on an Endorectal MRI Target Definition Model.

OBJECTIVES: To assess the outcome of patients treated with a dose-adapted salvage radiotherapy (SRT) protocol based on an endorectal magnetic resonance imaging (erMRI) failure definition model after radical prostatectomy (RP). METHODS: We report on 171 relapsing patients after RP who had undergone an erMRI before SRT. 64 Gy were prescribed to the prostatic bed with, in addition, a boost of 10 Gy to the suspected local relapse as detected on erMRI in 131 patients (76.6%). RESULTS: The 3-year biochemical relapse-free survival (bRFS), local relapse-free survival, distant metastasis-free survival, cancer-specific survival, and overall survival were 64.2±4.3%, 100%, 85.2±3.2%, 100%, and 99.1±0.9%, respectively. A PSA value >1 ng/mL before salvage (P=0.006) and an absence of biochemical progression during RT (P=0.001) were both independently correlated with bRFS on multivariate analysis. No significant difference in 3-year bRFS was observed between the boost and no-boost groups (68.4±4.6% vs. 49.7±10%, P=0.251). CONCLUSIONS: A PSA value >1 ng/mL before salvage and a biochemical progression during RT were both independently correlated with worse bRFS after SRT. By using erMRI to select patients who are most likely expected to benefit from dose-escalated SRT protocols, this dose-adapted SRT approach was associated with good biochemical control and outcome, serving as a hypothesis-generating basis for further prospective trials aimed at improving the therapeutic ratio in the salvage setting.

Comparison of the incidence of osteoradionecrosis with conventional radiotherapy and intensity-modulated radiotherapy.

BACKGROUND: Modern techniques of radiotherapy are supposed to decrease the incidence of osteoradionecrosis of the mandible (ORNM). The purpose of this study was to compare the incidence of ORNM after intensity-modulated radiotherapy (IMRT) in comparison to conventional 3D conformal radiotherapy techniques (conventional RT). METHODS: We conducted a retrospective study of consecutive unselected patients treated in a single institution between 2002 and 2012. To minimize confounding effects, only patients with oropharyngeal carcinoma without surgery of the primary site were included. RESULTS: The cohorts included 145 patients in the conventional RT group and 89 patients in the IMRT group. Total incidence rate of ORNM was similar for both groups with rates of 11% versus 10% (n = 16 for conventional RT and n = 9 for IMRT; p = 1.0). Subanalysis revealed more ORNM in T4 classified lesions with IMRT (p = .007). Analysis of different risk factors showed no statistically significant difference between ORNM and no-ORNM patients. CONCLUSION: We found no reduction in ORNM with IMRT. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.