Clinical outcomes in relapsed oropharyngeal cancer after definitive (chemo) radiotherapy.

OBJECTIVES: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity-modulated (chemo)radiotherapy [(C)RT]. MATERIALS AND METHODS: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end-point was post-failure survival (PFS). RESULTS: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)-negative; n = 16 HPV-positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two-year PFS for the entire population was 30.6%; 20.5% for HPV-negative and 43.8% for HPV-positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11). CONCLUSION: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV-positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS.

Radical cancer treatment is safe during COVID-19: the real-world experience of a large London-based Comprehensive Cancer Centre during the first wave.

BACKGROUND: During the COVID pandemic, there was a paucity of data to support clinical decision-making for anticancer treatments. We evaluated the safety of radical treatments which were delivered whilst mitigating the risks of concurrent COVID-19 infection. METHODS: Using descriptive statistics, we report on the characteristics and short-term clinical outcomes of patients undergoing radical cancer treatment during the first COVID-19 wave compared to a similar pre-pandemic period. RESULTS: Compared to 2019, the number of patients undergoing radical treatment in 2020 reduced by: 28% for surgery; 18% for SACT; and 10% for RT. Within SACT, 36% received combination therapy, 35% systemic chemotherapy, 23% targeted treatments, 5% immunotherapy and 2% biological therapy. A similar proportion of RT was delivered in 2019 and 2020 (53% vs. 52%). Oncological outcomes were also similar to pre-COVID-19. The COVID-19 infection rates were low: 12 patients were positive pre surgery (1%), 7 post surgery (<1%), 17 SACT patients (2%) and 3 RT patients (<1%). No COVID-19-related deaths were reported. CONCLUSIONS: Whilst there were fewer patients receiving radical anticancer treatments, those who did receive treatment were treated in a safe environment. Overall, cancer patients should have the confidence to attend hospitals and be reassured of the safety measures implemented.

The Impact of COVID-19 on the Delivery of Systemic Anti-Cancer Treatment at Guy's Cancer Centre.

BACKGROUND: This study aimed to assess the outcome of cancer patients undergoing systemic anti-cancer treatment (SACT) at our centre to help inform future clinical decision-making around SACT during the COVID-19 pandemic. METHODS: Patients receiving at least one episode of SACT for solid tumours at Guy's Cancer Centre between 1 March and 31 May 2020 and the same period in 2019 were included in the study. Data were collected on demographics, tumour type/stage, treatment type (chemotherapy, immunotherapy, biological-targeted) and SARS-CoV2 infection. RESULTS: A total of 2120 patients received SACT in 2020, compared to 2449 in 2019 (13% decrease). From 2019 to 2020, there was an increase in stage IV disease (62% vs. 72%), decrease in chemotherapy (42% vs. 34%), increase in immunotherapy (6% vs. 10%), but similar rates of biologically targeted treatments (37% vs. 38%). There was a significant increase in 1st and 2nd line treatments in 2020 (68% vs. 81%; p < 0.0001) and reduction in 3rd and subsequent lines (26% vs. 15%; p = 0.004) compared to 2019. Of the 2020 cohort, 2% patients developed SARS-CoV2 infections. CONCLUSIONS: These real-world data from a tertiary Cancer Centre suggest that despite the challenges faced due to the COVID-19 pandemic, SACT was able to be continued without any significant effects on the mortality of solid-tumour patients. There was a low rate (2%) of SARS-CoV-2 infection which is comparable to the 1.4%-point prevalence in our total cancer population.

The impact of Human Papilloma Virus status on the prediction of head and neck cancer chemoradiotherapy outcomes using the pre-treatment apparent diffusion coefficient.

OBJECTIVE: To determine the impact of Human Papilloma Virus (HPV) oropharyngeal cancer (OPC) status on the prediction of head and neck squamous cell cancer (HNSCC) chemoradiotherapy (CRT) outcomes with pre-treatment quantitative diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: Following ethical approval, 65 participants (53 male, age 59.9 ± 7.86) underwent pre-treatment DW-MRI in this prospective cohort observational study. There were 46 HPV OPC and 19 other HNSCC cases with Stage III/IV HNSCC. Regions of interest (ROIs) (volume, largest area, core) at the primary tumour (n = 57) and largest pathological node (n = 59) were placed to analyse ADCmean and ADCmin. Unpaired t-test or Mann-Whitney test evaluated the impact of HPV OPC status and clinical parameters on their prediction of post-CRT 2 year locoregional and disease-free survival (LRFS and DFS). Multivariate logistic regression compared significant variables with 2 year outcomes. RESULTS: On univariate analysis of all participants, the primary tumour area ADCmean was predictive of 2 year LRFS (p = 0.04). However, only the HPV OPC diagnosis (LFRS p = 0.03; DFS p = 0.02) predicted outcomes on multivariate analysis. None of the pre-treatment ADC values were predictive of 2 year DFS in the HPV OPC subgroup (p = 0.21-0.68). Amongst participants without 2 year disease-free survival, HPV-OPC was found to have much lower primary tumour ADCmean values than other HNSCC. CONCLUSION: Knowledge of HPV OPC status is required in order to determine the impact of the pre-treatment ADC values on post-CRT outcomes in HNSCC. ADVANCES IN KNOWLEDGE: Pre-treatment ADCmean and ADCmin values acquired using different ROI methods are not predictive of 2 year survival outcomes in HPV OPC.

Risk stratified follow up for head and neck cancer patients - An evidence based proposal.

Head and neck squamous cell carcinoma (HNSCC) has a significant impact on patients' quality of life and treatment can be associated with severe morbidity. Following completion of treatment, patients are followed up in order to detect potentially salvageable recurrences and to manage long-term toxicities. In recent years, a growing interest has been given to risk stratified follow-up interventions to prevent and detect recurrences and manage treatment toxicities in other tumour sites as well as to transfer some of that care to community services. We review the literature for HNSCC and propose a risk stratified follow up protocol to address these issues and assist clinicians in decision making. A shift in patterns of care is suggested in order to provide a basis to improve care for HNSCC patients after complete response to primary treatment.

TNM 8 staging is a better prognosticator than TNM 7 for patients with locally advanced oral cavity squamous cell carcinoma treated with surgery and post-operative radiotherapy.

PURPOSE: To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7. MATERIAL AND METHODS: Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months. RESULTS: Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis. CONCLUSION: TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients.

Safety and Treatment Outcomes of Nivolumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Retrospective Multicenter Cohort Study.

Nivolumab is an anti-PD-1 monoclonal antibody currently used as immunotherapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with evidence of disease progression after platinum-based chemotherapy. This study evaluates real-world safety and treatment outcomes of non-trial nivolumab use. A retrospective multicenter cohort study of patients with recurrent/metastatic HNSCC treated with nivolumab between January 2017 and March 2020 was performed. Overall, 123 patients were included. The median age was 64 years, the majority of patients were male (80.5%) and had a smoking history (69.9%). Primary outcomes included overall response rate (ORR) of 19.3%, median progression-free survival (PFS) of 3.9 months, 1-year PFS rate of 16.8%, a median overall survival (OS) of 6.5 months and 1-year OS rate of 28.6%. These results are comparable to the CHECKMATE-141 study. Of 27 patients who had PD-L1 status tested, positive PD-L1 status did not significantly affect PFS (p = 0.86) or OS (p = 0.84). Nivolumab was well tolerated with only 15.1% experiencing immune-related toxicities (IRT) and only 6.7% of patients stopping due to toxicity. The occurrence of IRT appeared to significantly affect PFS (p = 0.01) but not OS (p = 0.07). Nivolumab in recurrent/metastatic HNSCC is well tolerated and may be more efficacious in patients who develop IRT.

Factors Affecting COVID-19 Outcomes in Cancer Patients: A First Report From Guy's Cancer Center in London.

Background: There is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 due to the lack of large studies. Methods: We used data from a single large UK Cancer Center to assess the demographic/clinical characteristics of 156 cancer patients with a confirmed COVID-19 diagnosis between 29 February and 12 May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. Results: 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with a severe case of the disease. An initial cancer diagnosis >24 months before COVID-19 [OR: 1.74 (95% CI: 0.71-4.26)], presenting with fever [6.21 (1.76-21.99)], dyspnea [2.60 (1.00-6.76)], gastro-intestinal symptoms [7.38 (2.71-20.16)], or higher levels of C-reactive protein [9.43 (0.73-121.12)] were linked with greater COVID-19 severity. During a median follow-up of 37 days, 34 patients had died of COVID-19 (22%). Being of Asian ethnicity [3.73 (1.28-10.91)], receiving palliative treatment [5.74 (1.15-28.79)], having an initial cancer diagnosis >24 months before [2.14 (1.04-4.44)], dyspnea [4.94 (1.99-12.25)], and increased CRP levels [10.35 (1.05-52.21)] were positively associated with COVID-19 death. An inverse association was observed with increased levels of albumin [0.04 (0.01-0.04)]. Conclusions: A longer-established diagnosis of cancer was associated with increased severity of infection as well as COVID-19 death, possibly reflecting the effects a more advanced malignant disease has on this infection. Asian ethnicity and palliative treatment were also associated with COVID-19 death in cancer patients.

One Piece of the Jigsaw for the Cancer Recovery Strategy: Prevalence of COVID-19 in Patients With Cancer.

COVID-19 has forced governments to make drastic changes to healthcare systems. To start making informed decisions about cancer care, we need to understand the scale of COVID-19 infection. Therefore, we introduced swab testing for patients visiting Guy's Cancer Centre. Our Centre is one of the largest UK Cancer Centers at the epicenter of the UK COVID-19 epidemic. The first COVID-19 positive cancer patient was reported on 29 February 2020. We analyzed data from 7-15 May 2020 for COVID-19 tests in our cancer patients. 2,647 patients attended for outpatient, chemotherapy, or radiotherapy appointments. 654 were swabbed for COVID-19 (25%). Of those tested, 9 were positive for COVID-19 (1.38%) of which 7 were asymptomatic. Cancer service providers will need to understand their local cancer population prevalence. The absolute priority is that cancer patients have the confidence to attend hospitals and be reassured that they will be treated in a COVID-19 managed environment.

Analyzing oropharyngeal cancer survival outcomes: a decision tree approach.

OBJECTIVES: To analyze survival outcomes in patients with oropharygeal cancer treated with primary intensity modulated radiotherapy (IMRT) using decision tree algorithms. METHODS: A total of 273 patients with newly diagnosed oropharyngeal cancer were identified between March 2010 and December 2016. The data set contained nine predictor variables and a dependent variable (overall survival (OS) status). The open-source R software was used. Survival outcomes were estimated by Kaplan-Meier method. Important explanatory variables were selected using the random forest approach. A classification tree that optimally partitioned patients with different OS rates was then built. RESULTS: The 5 year OS for the entire population was 78.1%. The top three important variables identified were HPV status, N stage and early complete response to treatment. Patients were partitioned in five groups on the basis of these explanatory variables. CONCLUSION: The proposed classification tree could help to guide future research in oropharyngeal cancer field. ADVANCES IN KNOWLEDGE: Decision tree method seems to be an appropriate tool to partition oropharyngeal cancer patients.

Clinical evaluation of tumour-infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.

Clinical evaluation of tumour-infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma AIMS: The majority of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OpSCC) have favourable survival outcomes, but a significant minority of individuals will die of their disease. There are currently no definitive criteria with which to identify HPV-associated OpSCC patients with poor outcomes. Recent reports suggest that quantitative evaluation of T-cell subpopulations in OpSCC may be of prognostic value, but the methods used have limited utility in a clinical diagnostic setting. We therefore sought to determine the clinical prognostic utility of tumour-infiltrating lymphocyte (TIL) evaluation in patients with HPV-associated OpSCC within the context of a diagnostic histopathology setting. METHODS AND RESULTS: Representative diagnostic haematoxylin and eosin (H&E)-stained slides from 232 consecutive HPV-associated OpSCC patients were classified as containing a high (TILHi ; diffuse, lymphocytes in >80% of tumour and stroma), moderate (TILMod ; patchy, present in 20-80% of tumour and stroma) or low (TILLo ; sparse or absent, present in <20% of tumour and stroma) TILs. Interobserver reliability was assessed, and TIL category was then correlated with overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses showed statistically significant differences in OS and DFS estimates when TILHi and TILMod patients were compared with TILLo patients (P < 0.0001 for TILHi versus TILLo ; P < 0.0001 for TILMod versus TILLo ). Statistical significance was retained when TILHi and TILMod patients were grouped into a single category (TILHi ) and compared with TILLo patients (P < 0.0001). CONCLUSION: We demonstrate the prognostic utility of TILs in patients with HPV-associated OpSCC in clinical practice. A binary system classifying HPV-associated OpSCC into TILHi and TILLo on the basis of routine H&E staining stratifies patients into those with potentially favourable and unfavourable survival outcomes, respectively.

Outcomes of salvage surgery for the oropharynx and larynx: a contemporary experience in a UK Cancer Centre.

INTRODUCTION: The purpose of this study was to review our recent experience of salvage surgery, comparing larynx and oropharynx recurrence patterns. METHODS: A single centre, retrospective review of salvage surgery for recurrent head and neck cancer including patients between 2008 and 2016. RESULTS: 61 patients were identified, 36 underwent salvage laryngectomy and 25 received oropharyngeal resections. The median overall survival of oropharyngeal recurrent tumors was 26 months (95% CI 15-118 months) and for laryngeal tumors was 23 months (95% CI 11-38 months), p = 0.1008. There was a significant overall survival benefit in patients with negative resection margin. The median survival in the negative margin group was 38 months (95% CI 25-108 months) compared to the positive margin group, 9 months (95% CI 5-15 months), p < 0.0001. CONCLUSION: Survival results following surgical salvage in the larynx and oropharynx appear to be similarly poor. Those patients with clear margins appear to have a significantly better prognosis.

Osteoradionecrosis following treatment for head and neck cancer and the effect of radiotherapy dosimetry: the Guy's and St Thomas' Head and Neck Cancer Unit experience.

OBJECTIVES: To analyze clinical features, dosimetric parameters, and outcomes of osteoradionecrosis (ORN). STUDY DESIGN: Thirty-six patients with ORN who had been previously treated with radiotherapy (RT) were retrospectively identified between January 2009 and April 2014. ORN volumes were contoured on planning computed tomography (CT) scans. Near maximum dose (D2%), minimum dose (Dmin), mean dose (Dmean), and percentage of bone volume receiving 50 Gy (V50) were examined. Clinical and dosimetric variables were considered to compare ORN resolution versus ORN persistence. RESULTS: Median interval time from end of RT to development of ORN was 6 months. Of the ORN cases, 61% were located in the mandible. Dmean to affected bone was 57.6 Gy, and 44% had a D2% 65 Gy or greater. Smoking was associated with ORN persistence on univariate analysis, but no factors were found to impact ORN resolution or progression on logistic regression. CONCLUSIONS: Prevention strategies for ORN development should be prioritized. Dose-volume parameters could have a role in preventing ORN.

Parathyroid carcinoma.

PURPOSE OF REVIEW: This article highlights recent advances in our understanding of the incidence, epidemiology, clinical presentation, evaluation, diagnosis, treatment, and prognosis of parathyroid carcinoma. RECENT FINDINGS: The prevalence of parathyroid carcinoma is approximately 0.005% of all cancers. Therefore, parathyroid carcinoma is one of the rarest malignancies known. Patients with parathyroid carcinoma present with clinical symptoms of hypercalcaemia as these cancers are usually hormonally functional. It is not uncommon that patients present with complications of profound hypercalcaemia because of an elevated parathyroid hormone. Parathyroid carcinoma is difficult to diagnose preoperatively unless patients present with metastatic disease. Serum calcium often exceeds 14 mg/dl and serum parathyroid hormone is significantly elevated commonly between three and 10 times of the upper limit. Fine needle aspiration is not recommended because of the risk of parathyromatosis. Treatment includes surgery as a primary form of therapy and this usually follows with postoperative radiotherapy, although its use remains controversial. SUMMARY: Patients with parathyroid carcinoma should undergo adequate surgical excision with an attempt of preserving vital structures such as the recurrent laryngeal nerve. Often en bloc resection of the ipsilateral thyroid lobe with comprehensive level VI dissection is required. Postoperative radiotherapy should be considered in most cases.

(18)F-FDG PET/CT to assess response and guide risk-stratified follow-up after chemoradiotherapy for oropharyngeal squamous cell carcinoma.

PURPOSE: To evaluate the use of (18)F-FDG PET/CT as the principal investigation to assess tumour response, to determine the need for further surgery and to guide follow-up following radical chemoradiotherapy for stage III/IV oropharyngeal squamous cell carcinoma (OPSCC). METHODS: A retrospective analysis was undertaken in 146 patients treated at our centre with radical chemoradiotherapy for OPSCC and who had a PET/CT scan to assess response. According to the PET/CT findings, patients were divided into four groups and recommendations: (1) complete metabolic response (enter clinical follow-up); (2) low-level uptake only (follow-up PET/CT scan in 12 weeks); (3) residual uptake suspicious for residual disease (further investigation with or without neck dissection); and (4) new diagnosis of distant metastatic disease (palliative treatment options). RESULTS: The initial PET/CT scan was performed at a median of 12.4 weeks (range 4.3 - 21.7 weeks) following treatment. Overall sensitivity and specificity rates were 92.0 % (74.0 - 99.0 %) and 85 % (77.5 - 90.9 %). Of the 146 patients, 90 (62 %) had a complete response and had estimated 3-year overall and disease-free survival rates of 91.9 % (85.6 - 98.2 %) and 85.6 % (78.0 - 93.2 %), respectively, 17 (12 %) had residual low-level uptake only (with two having confirmed residual disease on subsequent PET/CT, both surgically salvaged), 30 (21 %) had suspicious residual uptake (12 proceeded to neck dissection; true positive rate at surgery 33 %). HPV-positive patients with reassuring PET/CT findings had an estimated 3-year progression-free survival rate of 91.7 % (85.2 - 98.2 %), compared with 66.2 % (41.5 - 90.9 %) of HPV-negative patients. CONCLUSION: A strategy of using PET/CT results alongside clinical examination to help select patients for salvage surgery appears successful. Despite a complete response on the 12-week PET/CT scan, HPV-negative patients have a significant risk of disease relapse in the following 2 years and further studies to assess whether surveillance imaging in this group could improve outcomes are warranted.

Analysis of loco-regional failures in head and neck cancer after radical radiation therapy.

OBJECTIVES: To investigate the anatomical distribution of loco-regional treatment failures (LRF) in patients with head and neck squamous cell carcinoma (HNSCC) in relation to clinical target volume (CTV) delineation. MATERIALS AND METHODS: 56 patients with LRF were retrospectively identified. Patients were previously treated with radical intensity modulated radiotherapy (IMRT) +/- chemotherapy. Target volumes include gross tumour volume (GTV), its volumetric expansion of 10mm (GTV-HD), CTV high dose (CTV-HD) delineated by anatomic expansion from GTV and CTV low dose (CTV-LD) defined to receive a prophylactic dose. LRF were evaluated by PET-CT or CT scan. We analysed the association between sites of LRF and target volumes and dosimetry, using image co-registration. Based on percentage of volume that received 95% of prescribed dose, LRF were classified as in-field, marginal or out-field. RESULTS: Median interval time from end of treatment to LRF was 186days. 65 (95.6%) LRF were classified as in-field. Considering primary target volumes, 40 (58.8%) LRF occurred inside GTV, 13 (19.1%) in GTV-HD and 7 (10.3%) in CTV-HD. The overall 1-year and 2-year post-failure survival (PFS) was 45.8% and 24.2%, respectively. Post radiation LRF managed with salvage surgery had a significantly higher median PFS when compared with palliative treatments (p=0.003). CONCLUSIONS: The majority of LRF occurred within GTV/GTV-HD, suggesting it is safe to reduce the CTV to a volumetric expansion. Given the low incidence of geographical misses, future studies should be directed towards dose escalation of high-risk volumes. Potential reduction of RT-related toxicity with volumetric expansion could facilitate salvage surgery.

Controversies in small cell carcinoma of the head and neck: Prophylactic cranial irradiation (PCI) after primary complete initial remission.

Small cell carcinoma of head and neck region (SmCCHN) represents a rare entity and its management remains a significant clinical challenge. Complete initial response to primary therapy poses a difficult and controversial scenario for radiation oncologists. Prophylactic cranial irradiation (PCI) has long been established in the management of small cell lung cancer; however, its role in SmCCHN is still called into question. The rationale behind PCI lies in the eradication of possible micro-metastatic brain disease, which is often documented in this type of cancer. No randomized trials on this topic are available. This review, based on 20 retrospective studies, addresses the controversies in the use of PCI in SmCCHN management.

Biphenotypic human papillomavirus-associated head and neck squamous cell carcinoma: a report of two cases.

Human papillomavirus-associated oropharyngeal squamous cell carcinoma is now recognised as a subtype of head and neck cancer with distinct clinical, molecular and histological characteristics. The majority of these carcinomas are of non-keratinising squamous type but there is a growing number of histomorphologic variants of this disease. Here we describe the clinical, histomorphologic and immunophenotypic features of two cases of human papillomavirus-associated oropharyngeal squamous cell carcinoma demonstrating a clearly delineated biphasic differentiated and undifferentiated phenotype.