Novel Strategies for Managing Retropharyngeal Lymph Node Metastases in Head and Neck and Thyroid Cancer with Transoral Robotic Surgery (TORS).

Retropharyngeal metastases are encountered in a variety of head and neck malignancies, imposing significant surgical challenges owing to their distinct location and proximity to neurovascular structures. Radiotherapy is the recommended treatment in most cases owing to its oncological efficacy. However, retropharyngeal irradiation affects the superior pharyngeal constrictor muscles and parotid glands, with the potential for long-term dysphagia and xerostomia. A younger oropharyngeal and thyroid cancer patient demographic is trending, fueling interest in treatment de-escalation strategies. Consequently, reducing radiotoxicity and its long-term effects is of special relevance in modern head and neck oncology practice. Through its unique ability to safely extirpate these traditionally difficult-to-access retropharyngeal lymph nodes via a natural orifice, TransOral Robotic Surgery (TORS) can considerably lower the surgical morbidity of retropharyngeal lymph node dissection (RPLND), compared with current existing approaches. This review summarizes the latest developments in the field, exposing current research gaps and discusses specific clinical settings where TORS could enable treatment de-escalation. In early-stage node-negative oropharyngeal cancer, single-modality surgical treatment with TORS RPLND may improve risk stratification of metastasis and recurrence in this region. TORS RPLND is also a potentially viable treatment option in salvage of an isolated retropharyngeal node recurrence or in the primary setting of a thyroid malignancy with a single positive retropharyngeal node. In time, TORS RPLND may provide an alternative de-escalation strategy in these three scenarios. However, with the reported morbidities, further prospective trials with long-term follow-up data are required to prove oncological safety and functional benefits over existing strategies.

Second-look PET-CT following an initial incomplete PET-CT response to (chemo)radiotherapy for head and neck squamous cell carcinoma.

OBJECTIVES: The limited positive predictive value of an incomplete response on PET-CT following (chemo)radiotherapy for head and neck squamous cell carcinoma (HNSCC) means that the optimal management strategy remains uncertain. The aim of the study is to assess the utility of a 'second-look' interval PET-CT. METHODS: Patients with HNSCC who were treated with (chemo)radiotherapy between 2008 and 2017 and underwent (i) baseline and (ii) response assessment PET-CT and (iii) second-look PET-CT following incomplete (positive or equivocal scan) response were included. Endpoints were conversion rate to complete response (CR) and test characteristics of the second-look PET-CT. RESULTS: Five hundred sixty-two patients with HNSCC underwent response assessment PET-CT at a median of 17 weeks post-radiotherapy. Following an incomplete response on PET-CT, 40 patients underwent a second-look PET-CT at a median of 13 weeks (range 6-25) from the first response PET-CT. Thirty-four out of 40 (85%) patients had oropharyngeal carcinoma. Twenty-four out of 40 (60%) second-look PET-CT scans converted to a complete locoregional response. The primary tumour conversion rate was 15/27 (56%) and the lymph node conversion rate was 14/19 (74%). The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the second-look PET-CT were 75%, 75%, 25% and 96% for the primary tumour and 100%, 92%, 40% and 100% for lymph nodes. There were no cases of progression following conversion to CR in the primary site or lymph nodes. CONCLUSIONS: The majority of patients who undergo a second-look PET-CT convert to a CR. The NPV of a second-look PET-CT is high, suggesting the potential to avoid surgical intervention. KEY POINTS: • PET-CT is a useful tool for response assessment following (chemo)radiotherapy for head and neck squamous cell carcinoma. • An incomplete response on PET-CT has a limited positive predictive value and optimal management is uncertain. • These data show that with a 'second-look' interval PET-CT, the majority of patients convert to a complete metabolic response. When there is doubt about clinical and radiological response, a 'second-look' PET-CT can be used to spare patients unnecessary surgical intervention.

Impact of choice of feeding tubes on long-term swallow function following chemoradiotherapy for oropharyngeal carcinoma.

Background: Prior reports have raised concerns that a prophylactic gastrostomy may be detrimental to long-term swallow function. This study evaluates patient-reported swallow function following chemoradiotherapy for oropharyngeal carcinoma in relation to the use of a prophylactic gastrostomy or nasogastric (NG) tube as required. Material and methods: The MD Anderson Dysphagia Inventory (MDADI) was posted to 204 disease-free patients at least 2 years following chemoradiotherapy for oropharyngeal carcinoma between 2010 and 2014. Results: Overall, 181/204 (89%) patients returned questionnaire at a median of 34 months post-treatment. 97/181 (54%) and 84/181 (46%) were managed with an approach of a prophylactic gastrostomy or NG tube as required, respectively. A prophylactic gastrostomy was associated with higher rates of enteral feeding (92% vs. 58%, p < .001), lower median percentage weight loss (7.0% vs. 9.4%, p < .001), increased duration of enteral feed (median 3.3 vs. 1.1 months, p < .001). There was no significant difference in patient-reported swallow function measured by MDADI summary scores and subscales for patients managed with an approach of prophylactic gastrostomy or NG as required. Duration of enteral feed correlated negatively with composite MDADI scores. A subgroup of 116/181 (64%) patients were documented as having been offered a choice of enteral feeding approach and therefore can be considered to represent clinical equipoise; there were no significant differences in MDADI scores according to route. Conclusions: Despite concern regarding the use of a prophylactic gastrostomy in prior studies, the approaches of using a prophylactic gastrostomy or an NG tube as required to support patients during/after chemoradiotherapy for oropharyngeal carcinoma were associated with similar long-term swallow outcomes.

The feasibility of atlas-based automatic segmentation of MRI for H&N radiotherapy planning.

Atlas-based autosegmentation is an established tool for segmenting structures for CT-planned head and neck radiotherapy. MRI is being increasingly integrated into the planning process. The aim of this study is to assess the feasibility of MRI-based, atlas-based autosegmentation for organs at risk (OAR) and lymph node levels, and to compare the segmentation accuracy with CT-based autosegmentation. Fourteen patients with locally advanced head and neck cancer in a prospective imaging study underwent a T1-weighted MRI and a PET-CT (with dedicated contrast-enhanced CT) in an immobilization mask. Organs at risk (orbits, parotids, brainstem, and spinal cord) and the left level II lymph node region were manually delineated on the CT and MRI separately. A 'leave one out' approach was used to automatically segment structures onto the remaining images separately for CT and MRI. Contour comparison was performed using multiple positional metrics: Dice index, mean distance to conformity (MDC), sensitivity index (Se Idx), and inclusion index (Incl Idx). Automatic segmentation using MRI of orbits, parotids, brainstem, and lymph node level was acceptable with a DICE coefficient of 0.73-0.91, MDC 2.0-5.1mm, Se Idx 0.64-0.93, Incl Idx 0.76-0.93. Segmentation of the spinal cord was poor (Dice coefficient 0.37). The process of automatic segmentation was significantly better on MRI compared to CT for orbits, parotid glands, brainstem, and left lymph node level II by multiple positional metrics; spinal cord segmentation based on MRI was inferior compared with CT. Accurate atlas-based automatic segmentation of OAR and lymph node levels is feasible using T1-MRI; segmentation of the spinal cord was found to be poor. Comparison with CT-based automatic segmentation suggests that the process is equally as, or more accurate, using MRI. These results support further translation of MRI-based segmentation methodology into clinicalpractice.

Alterations in anatomic and functional imaging parameters with repeated FDG PET-CT and MRI during radiotherapy for head and neck cancer: a pilot study.

BACKGROUND: The use of imaging to implement on-treatment adaptation of radiotherapy is a promising paradigm but current data on imaging changes during radiotherapy is limited. This is a hypothesis-generating pilot study to examine the changes on multi-modality anatomic and functional imaging during (chemo)radiotherapy treatment for head and neck squamous cell carcinoma (HNSCC). METHODS: Eight patients with locally advanced HNSCC underwent imaging including computed tomography (CT), Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT and magnetic resonance imaging (MRI) (including diffusion weighted (DW) and dynamic contrast enhanced (DCE)) at baseline and during (chemo)radiotherapy treatment (after fractions 11 and 21). Regions of interest (ROI) were drawn around the primary tumour at baseline and during treatment. Imaging parameters included gross tumour volume (GTV) assessment, SUVmax, mean ADC value and DCE-MRI parameters including Plasma Flow (PF). On treatment changes and correlations between these parameters were analysed using a Wilcoxon rank sum test and Pearson's linear correlation coefficient respectively. A p-value <0.05 was considered statistically significant. RESULTS: Statistically significant reductions in GTV-CT, GTV-MRI and GTV-DW were observed between all imaging timepoints during radiotherapy. Changes in GTV-PET during radiotherapy were heterogeneous and non-significant. Significant changes in SUVmax, mean ADC value, Plasma Flow and Plasma Volume were observed between the baseline and the fraction 11 timepoint, whilst only changes in SUVmax between baseline and the fraction 21 timepoint were statistically significant. Significant correlations were observed between multiple imaging parameters, both anatomical and functional; 20 correlations between baseline to the fraction 11 timepoint; 12 correlations between baseline and the fraction 21 timepoints; and 4 correlations between the fraction 11 and fraction 21 timepoints. CONCLUSIONS: Multi-modality imaging during radiotherapy treatment demonstrates early changes (by fraction 11) in both anatomic and functional imaging parameters. All functional imaging modalities are potentially complementary and should be considered in combination to provide multi-parametric tumour assessment, to guide potential treatment adaptation strategies. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN34165059 . Registered 2nd February 2015.

Multimodality imaging with CT, MR and FDG-PET for radiotherapy target volume delineation in oropharyngeal squamous cell carcinoma.

BACKGROUND: This study aimed to quantify the variation in oropharyngeal squamous cell carcinoma gross tumour volume (GTV) delineation between CT, MR and FDG PET-CT imaging. METHODS: A prospective, single centre, pilot study was undertaken where 11 patients with locally advanced oropharyngeal cancers (2 tonsil, 9 base of tongue primaries) underwent pre-treatment, contrast enhanced, FDG PET-CT and MR imaging, all performed in a radiotherapy treatment mask. CT, MR and CT-MR GTVs were contoured by 5 clinicians (2 radiologists and 3 radiation oncologists). A semi-automated segmentation algorithm was used to contour PET GTVs. Volume and positional analyses were undertaken, accounting for inter-observer variation, using linear mixed effects models and contour comparison metrics respectively. RESULTS: Significant differences in mean GTV volume were found between CT (11.9 cm(3)) and CT-MR (14.1 cm(3)), p < 0.006, CT-MR and PET (9.5 cm(3)), p < 0.0009, and MR (12.7 cm(3)) and PET, p < 0.016. Substantial differences in GTV position were found between all modalities with the exception of CT-MR and MR GTVs. A mean of 64 %, 74 % and 77 % of the PET GTVs were included within the CT, MR and CT-MR GTVs respectively. A mean of 57 % of the MR GTVs were included within the CT GTV; conversely a mean of 63 % of the CT GTVs were included within the MR GTV. CT inter-observer variability was found to be significantly higher in terms of position and/or volume than both MR and CT-MR (p < 0.05). Significant differences in GTV volume were found between GTV volumes delineated by radiologists (9.7 cm(3)) and oncologists (14.6 cm(3)) for all modalities (p = 0.001). CONCLUSIONS: The use of different imaging modalities produced significantly different GTVs, with no single imaging technique encompassing all potential GTV regions. The use of MR reduced inter-observer variability. These data suggest delineation based on multimodality imaging has the potential to improve accuracy of GTV definition. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN34165059 . Registered 2nd February 2015.

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.

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.

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.

Reciprocal human dendritic cell-natural killer cell interactions induce antitumor activity following tumor cell infection by oncolytic reovirus.

Oncolytic virotherapy may mediate antitumor effects via direct oncolysis or immune-mediated tumor regression. Although the ability of oncolytic viruses to generate adaptive antitumor immunity has been characterized, their interactions with the innate immune system are relatively unclear. Using a human in vitro system, this study investigates the innate immunological consequences of reovirus therapy and its potential to activate NK cell-mediated antitumor activity. Dendritic cells (DC) loaded with reovirus-infected human melanoma Mel888 cells (DC-MelReo), but not reovirus-infected tumor cells alone, induced IFN-gamma production within the NK cell population upon coculture with PBMC, in a cell-to-cell contact-dependent manner. DC-MelReo secreted the chemokines CCL2, 3, 4, 5, 7, 8, 11, and CXCL10; these culture supernatants induced NK cell chemotaxis. Coculture of DC-MelReo with purified NK cells induced reciprocal contact-dependent phenotypic DC maturation, while DC-MelReo elicited up-regulation of the activation marker CD69 on NK cells, in a partially contact and partially IL-12 dependent manner. Significantly, DC-MelReo induced NK cell cytotoxicity toward tumor cells by a type I IFN dependent mechanism. These data demonstrate that tumor infection by reovirus can act via DC to induce NK cell recruitment, activation, and cytotoxicity, along with reciprocal DC maturation. These findings suggest that reciprocal DC-NK cell interactions, following reovirus therapy, may play an important role in altering the immune milieu of the tumor microenvironment and mediating tumor regression.

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.

The feasibility of establishing a programme of adjuvant autologous vaccination for renal cell carcinoma.

OBJECTIVE: To report the results of a programme aimed at determining the feasibility of autologous renal cell carcinoma (RCC) tissue collection and vaccine preparation within the setting of a UK National Health Service Cancer Centre. PATIENTS AND METHODS: Patients undergoing nephrectomy for suspected renal tumours were identified from theatre lists between April 2005 and July 2007. Samples of tumour were freshly cut from nephrectomy specimens. If tissue collection failed the reason was recorded prospectively. Cell viability was assessed after sample sieving. Freeze-thaw lysates were prepared from viable tumour cells, and the immunogenicity tested by pulsing onto dendritic cells (DC). RESULTS: Of 84 patients, 83 had a histological diagnosis of RCC; samples were obtained from 29 of these 83 (35%). Reasons for failure in tissue collection included that the tumour was too small or haemorrhagic/necrotic, pre-surgical embolization, and difficulties with fresh tumour collection out of normal working hours. Viable tumour cells were obtained in 12 of the 29 samples (41%); no factor was able to predict the production of viable cells. Unmodified lysates did not activate DC. CONCLUSION: An autologous RCC vaccination programme might fail to generate vaccines for a substantial proportion of eligible patients in the setting of a clinical cancer centre.

Tumor infection by oncolytic reovirus primes adaptive antitumor immunity.

PURPOSE: Early clinical trials are under way exploring the direct oncolytic potential of reovirus. This study addresses whether tumor infection by reovirus is also able to generate bystander, adaptive antitumor immunity. EXPERIMENTAL DESIGN: Reovirus was delivered intravenously to C57BL/6 mice bearing lymph node metastases from the murine melanoma, B16-tk, with assessment of nodal metastatic clearance, priming of antitumor immunity against the tumor-associated antigen tyrosinase-related protein-2, and cytokine responses. In an in vitro human system, the effect of reovirus infection on the ability of Mel888 melanoma cells to activate and load dendritic cells for cytotoxic lymphocyte (CTL) priming was investigated. RESULTS: In the murine model, a single intravenous dose of reovirus reduced metastatic lymph node burden and induced antitumor immunity (splenocyte response to tyrosinase-related protein-2 and interleukin-12 production in disaggregated lymph nodes). In vitro human assays revealed that uninfected Mel888 cells failed to induce dendritic cell maturation or support priming of an anti-Mel888 CTL response. In contrast, reovirus-infected Mel888 cells (reo-Mel) matured dendritic cells in a reovirus dose-dependent manner. When cultured with autologous peripheral blood lymphocytes, dendritic cells loaded with reo-Mel induced lymphocyte expansion, IFN-gamma production, specific anti-Mel888 cell cytotoxicity, and cross-primed CD8+ T cells specific against the human tumor-associated antigen MART-1. CONCLUSION: Reovirus infection of tumor cells reduces metastatic disease burden and primes antitumor immunity. Future clinical trials should be designed to explore both direct cytotoxic and immunotherapeutic effects of reovirus.

Patients' experience of enteral feeding following (chemo) radiotherapy for head and neck cancer: A qualitative study.

BACKGROUND & AIMS: Enteral feeding is commonly required during radiotherapy treatment for head and neck cancer. Only limited qualitative research into head and neck cancer patients' experiences of enteral tube feeding has been undertaken. The aim of this qualitative study was to evaluate patients' experiences of EF and the surrounding decision making process. METHODS: Semi-structured, face-to face interviews were conducted with ten patients who had completed (chemo)radiotherapy/radiotherapy for head and neck cancer at a cancer centre in the North of England. Interviews were recorded, transcribed verbatim and analysed qualitatively using Thematic Analysis. RESULTS: Participants described the restrictions on daily living caused by enteral feeding tubes and enteral feeding. Despite these restrictions, participants recognised the value of the enteral feeding tube including its role in their survival and the importance of their involvement in decision making. Participants described coping mechanisms used to deal with the difficulties associated with enteral feeding. CONCLUSIONS: The results of this study provide a unique qualitative insight into the lived experiences of H&N cancer patients managed with enteral feeding and the impact of the decision making process. The results have relevance for professionals supporting this patient group with enteral feeding.

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.