"Why am I still suffering?": Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors following (chemo)radiotherapy.

Background: Late effects of cancer treatment, such as neurocognitive deficits and fatigue, can be debilitating. Other than head and neck-specific functional deficits such as impairments in swallowing and speech, little is known about survivorship after oropharyngeal cancer. This study examines the lived experience of fatigue and neurocognitive deficits in survivors of oropharyngeal squamous cell cancer and impact on their daily lives. Methods: This work is part of the multicentre mixed method ROC-oN study (Radiotherapy for Oropharyngeal Cancer and impact on Neurocognition), evaluating fatigue and neurocognitive function in patients following radiotherapy +/- chemotherapy for oropharyngeal cancer and impact on quality of life. Semi-structured interviews were conducted in adults treated with radiotherapy (+/-chemotherapy) for oropharyngeal squamous cell carcinoma >/=24 months from completing treatment. Reflexive thematic analysis performed. Results: 21 interviews (11 men and 10 women; median age 58 years and median time post-treatment 5 years) were conducted and analysed, yielding six themes: (1) unexpected burden of fatigue, (2) noticing changes in neurocognitive function, (3) the new normal, (4) navigating changes, (5)insufficient awareness and (6)required support. Participants described fatigue that persisted beyond the acute post-treatment period and changes in neurocognitive abilities across several domains. Paid and unpaid work, emotions and mood were impacted. Participants described navigating the new normal by adopting self-management strategies and accepting external support. They reported lack of recognition of these late effects, being poorly informed and being unprepared. Follow-up services were thought to be inadequate. Conclusions: Fatigue and neurocognitive impairment were frequently experienced by survivors of oropharyngeal cancer, at least two years after treatment. Patients felt ill-prepared for these late sequelae, highlighting opportunities for improvement of patient information and support services.

Neurocognitive function following (chemo)radiotherapy for nasopharyngeal cancer and other head and neck cancers: A systematic review.

When radiotherapy is used in the treatment of head and neck cancers, the brain commonly receives incidental doses of radiotherapy with potential for neurocognitive changes and subsequent impact on quality of life. This has not been widely investigated to date. A systematic search of MEDLINE, EMBASE, Psycinfo Info and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases was conducted. Of 2077 records screened, 20 were eligible comprising 1308 patients. There were no randomised studies and 73.3% of included patients were from single center studies. IMRT was delivered in 72.6% of patients, and chemotherapy used in 61%. There was considerable heterogeneity in methods. Narrative synthesis was therefore carried out. Most studies demonstrated inferior neurocognitive outcomes when compared to control groups at 12 months and beyond radiotherapy. Commonly affected neurocognitive domains were memory and language which appeared related to radiation dose to hippocampus, temporal lobe, and cerebellum. Magnetic Resonance Imaging could be valuable in the detection of early microstructural and functional changes, which could be indicative of future neurocognitive changes. In studies investigating quality of life, the presence of neurocognitive impairment was associated with inferior quality of life outcomes. (Chemo)radiotherapy for head and neck cancer appears to be associated with a risk of long-term neurocognitive impairment. Few studies were identified, with substantial variation in methodology, thus limiting conclusions. High quality large prospective head and neck cancer studies using standardised, sensitive, and reliable neurocognitive tests are needed.

Accuracy of Response Assessment FDG PET-CT Post (Chemo)Radiotherapy in HPV Negative Oropharynx Squamous Cell Carcinoma.

Background: Data on the accuracy of response assessment 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) following (chemo)radiotherapy in patients with oropharynx squamous cell carcinoma (OPSCC) is predominantly based on HPV-positive disease. There is a paucity of data for HPV-negative disease, which has a less favourable prognosis. Methods: 96 patients treated with (chemo)radiotherapy for HPV-negative OPSCC with baseline and response assessment FDG PET-CT between 2013−2020, were analysed. PET-CT response was classified as negative, equivocal, or positive based on qualitative reporting. PET-CT response categories were analysed with reference to clinicopathological outcomes. Test characteristics were evaluated, comparing negative results to equivocal and positive results together. Post-test probabilities were calculated separately for positive and equivocal or negative results. Results: Median follow-up was 26 months. The negative predictive value of a negative scan was 93.7 and 93.2%, respectively, for primary tumour and nodal disease. For a negative scan, the post-test probability was 0.06 for primary and 0.07 for nodal disease. The post-test probability of an equivocal scan was 0.51 and 0.72 for primary and lymph node, respectively. The post-test probability of a positive scan approached 1. For patients with/without a negative scan, two-year overall survival and progression-free survival were 83% versus 30% and 79% versus 17% (p < 0.001), respectively. Conclusion: The NPV of a negative response assessment PET-CT in HPV-negative OPSCC is high, supporting a strategy of clinical monitoring. Contrasting with the published literature for HPV-positive OPSCC, an equivocal response scan was associated with a moderate rate of residual disease.

Similar long-term swallowing outcomes for accelerated, mildly-hypofractionated radiotherapy compared to conventional fractionation in oropharyngeal cancer: A multi-centre study.

BACKGROUND AND PURPOSE: There is renewed interest in hypofractionated radiotherapy, but limited data and a lack of consensus to support use for head and neck cancer. In this multicentre analysis we compared outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with conventional and accelerated, mildly hypofractionated radiotherapy without chemotherapy. MATERIALS AND METHODS: A multi-centre, observational study of consecutive OPSCCs treated between 2015 and 2018. Patients underwent curative-intent radiotherapy (oropharyngeal and bilateral neck) using conventionally fractionated (70 Gy in 35 fractions over 7 weeks, n = 97) or accelerated, mildly hypofractionated (65-66 Gy in 30 fractions over 6 weeks, n = 136) radiotherapy without chemotherapy. Locoregional control (LRC) and overall survival (OS) were compared. Patients alive and cancer-free at a minimum of 2 years post-radiotherapy (n = 151, 65%) were sent an MD Anderson Dysphagia Inventory (MDADI) questionnaire to assess swallow function. RESULTS: LRC and OS were similar across schedules (p = 0.78 and 0.95 respectively, log-rank test). Enteral feeding rates during radiotherapy appeared higher in the 7-week group though this did not reach statistical significance (59% vs 48%, p = 0.08). Feeding rates were similar at 1 year post radiotherapy for both groups (10% vs 6%, p = 0.27). 107 patients returned MDADI questionnaires (71%); there were no differences between the 6- and 7-week groups for median global (60.0 vs 60.0, p = 0.99) and composite (65.8 vs 64.2, p = 0.44) MDADI scores. CONCLUSION: Patients with OPSCC treated with radiotherapy alone have similar swallowing outcomes, LRC and OS following accelerated, mild hypofractionation and standard fractionation schedules, supporting its use as a standard-of-care option for patients unsuitable for concurrent chemotherapy.

Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer.

PURPOSE: There is a need to refine the selection of patients with oropharyngeal squamous cell carcinoma (OPSCC) for treatment de-escalation. We investigated whether pretreatment absolute lymphocyte count (ALC) predicted overall survival (OS) benefit from the addition of concurrent chemotherapy to radical radiotherapy. PATIENTS AND METHODS: This was an observational study of consecutive OPSCCs treated by curative-intent radiotherapy, with or without concurrent chemotherapy (n = 791) with external, independent validation from a separate institution (n = 609). The primary end point was OS at 5 years. Locoregional control (LRC) was assessed using competing risk regression as a secondary end point. Previously determined prognostic factors were used in a multivariable Cox proportional hazards model to assess the prognostic importance of ALC and the interaction between ALC and cisplatin chemotherapy use. RESULTS: Pretreatment ALC was prognostic for 5-year OS on multivariable analysis (hazard ratio [HR] 0.64; 95% CI, 0.42 to 0.98; P = .04). It also predicted benefit from the use of concurrent cisplatin chemotherapy, with a significant interaction between cisplatin chemotherapy and pretreatment ALC (likelihood ratio test, P = .04): higher ALC count reduced the 5-year OS benefit compared with radiotherapy alone (HR 2.53; 95% CI, 1.03 to 6.19; P = .043). This was likely driven by an effect on LRC up to 5 years (interaction subdistribution HR 2.29; 95% CI, 0.68 to 7.71; P = .094). An independent validation cohort replicated the OS (HR 2.53; 95% CI, 0.98 to 6.52; P = .055) and LRC findings (interaction subdistribution HR 3.43; 95% CI, 1.23 to 9.52; P = .018). CONCLUSION: For OPSCC, the pretreatment ALC is prognostic for OS and also predicts benefit from the addition of cisplatin chemotherapy to radiotherapy. These findings require prospective evaluation, and could inform the selection of good prognosis patients for a de-escalation trial.

Management of sinonasal cancers: Survey of UK practice and literature overview.

INTRODUCTION: Sinonasal malignancy is a rare and heterogenous disease, with limited evidence to guide management. This report summarises the findings of a UK survey and expert workshop discussion which took place to inform design of a proposed UK trial to assess proton beam therapy versus intensity-modulated radiation therapy. METHOD: A multidisciplinary working group constructed an online survey to assess current approaches within the UK to surgical and non-surgical practice. Head and neck clinical oncologists, ear nose and throat (ENT) and oral-maxillofacial (OMF) surgeons were invited to participate in the 42-question survey in September 2020. The Royal College of Radiologists Consensus model was adopted in establishing categories to indicate strength of response. An expert panel conducted a virtual workshop in November 2020 to discuss areas of disagreement. RESULTS: A survey was sent to 140 UK-based clinicians with 63 responses (45% response rate) from 30 centres, representing a broad geographical spread. Participants comprised 35 clinical oncologists (56%) and 29 surgeons (44%; 20 ENT and 9 OMF surgeons). There were variations in preferred sequence and combination of treatment modalities for locally advanced maxillary squamous cell carcinoma and sinonasal undifferentiated carcinoma. There was discordant surgical management of the orbit, dura, and neck. There was lack of consensus for radiotherapy in post-operative dose fractionation, target volume delineation, use of multiple dose levels and treatment planning approach to organs-at-risk. CONCLUSION: There was wide variation across UK centres in the management of sinonasal carcinomas. There is need to standardise UK practice and develop an evidence base for treatment.

Histiocytic sarcoma of the base of tongue treated with radical radiotherapy: A case report and review of the literature.

Histiocytic sarcoma (HS) is an exceedingly rare and aggressive neoplasm of lymphoid and haematopoietic tissues and expresses histological and phenotypical characteristics of mature histiocytes. There have only been a few cases of documented HS in the head and neck region. Whilst patients with HS often have nodal or disseminated disease, patients can present with localised disease. There are currently no established treatment guidelines, and reported cases of localised disease have been managed with primary surgery and adjuvant radiotherapy and/or chemotherapy. Here we present, the case of a 49 year old man with a HS of the base of tongue treated with radical radiotherapy to a dose of 60 Gy in 30 fractions, achieving disease free survival of greater than 5 years with minimal toxicity. To our knowledge, this is the first reported case of HS treated with radical radiotherapy, and suggests that when the potential morbidity of surgery for localised disease is significant, radiotherapy may represent an alternative treatment.

Incidence and patterns of retropharyngeal lymph node involvement in oropharyngeal carcinoma.

INTRODUCTION: The aim was to evaluate in oropharyngeal carcinoma the: (1) incidence and predictors of retropharyngeal (RP) lymph node (LN) involvement, (2) pattern of ipsilateral/bilateral/contralateral-only RP LNs (3) location of RP LNs in relation to contouring guidelines. METHODS: Single centre retrospective analysis of 402 patients with oropharyngeal carcinoma treated non-surgically between 2010 and 2017. All patients had a baseline FDG PET-CT and contrast-enhanced MRI and/or CT. All cases with reported abnormal RP LNs underwent radiology review. RESULTS: Abnormal RP LNs were identified in 40/402 (10%) of patients. On multivariate analysis, RP LN involvement was associated with posterior pharyngeal wall/soft palate primaries (OR 10.13 (95% CI 2.29-19.08), p = 0.002) and contralateral cervical LN involvement (OR 2.26 (95% CI 1.05-4.86), p = 0.036). T stage, largest LN size, levels of ipsilateral LN level involvement, HPV and smoking status did not predict risk. 5/402 (1.2%) patients had bilateral RP involvement. 3/402 patients (0.7%) had contralateral-only RP LNs. All patients with contralateral RP LNs had contralateral neck nodes or primary cancers extending across midline. In 5/40 (12.5%) cases with involved RP LNs, the RP LNs were superior to hard palate/upper edge of body of C1 vertebra. CONCLUSIONS: RP LNs were identified in 10% of oropharyngeal carcinoma patients, and were associated with contralateral neck disease and/or posterior pharyngeal wall/soft palate primary. Contralateral RP LN involvement was rare and associated with contralateral neck disease and/or primary crossing midline, suggesting potential for omission from target volumes for selected patients. Involvement of RP LNs close to the skull base highlights the need for generous elective outlining.

Retropharyngeal Lymph Node Involvement in Oropharyngeal Carcinoma: Impact upon Risk of Distant Metastases and Survival Outcomes.

The influence of retropharyngeal lymph node (RPLN) involvement on prognosis in oropharyngeal carcinoma remains poorly defined. The aim of this study was to assess the impact of RPLN involvement upon outcomes. A single-centre retrospective analysis of 402 patients with oropharyngeal carcinoma treated nonsurgically between 2010 and 2017 was performed. All had a baseline 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) PET-CT and contrast-enhanced MRI and/or CT. RPLN status was determined by radiology review of cases with reported abnormal RPLN. Multivariate backwards logistic regression was used to examine impact on outcomes of factors. Abnormal RPLNs were identified in 40/402 (10%) of patients. Median follow up was 42.9 months. RPLN involvement was associated with inferior 3 year outcomes for overall survival (OS) (67.1% vs. 79.1%, p = 0.006) and distant metastases-free survival (DMFS) (73.9% versus 88.0%, p = 0.011), with no significant difference in local control (81.6% vs. 87.7%, p = 0.154) or regional control (80.7% vs. 85.4%, p = 0.252). On multivariate analysis abnormal RPLN, no concurrent chemotherapy and ongoing smoking were associated with inferior DMFS and OS, while advanced T stage was also associated with inferior OS. In summary, RPLN involvement, present in 10% of patients, was an independent prognostic factor for the development of distant disease failure translating into inferior OS. These findings need confirmation in future studies.