Associations between Human Papillomavirus Status, Weight Change, and Survival of Oropharyngeal Cancer Patients.

This study examined associations between HPV status and weight change in oropharyngeal cancer (OPC). OPC patients receiving concurrent chemoradiotherapy in Toronto, Canada were included. Relationships were assessed between HPV status and weight loss grade (WLG, combining weight loss and current body mass index); weight change during treatment; and HPV status and WLG/weight change on overall (OS) and cancer-specific (CSS) survival. Of 717 patients, WLG pre-radiation was less severe among HPV-positive compared to HPV-negative, though weight loss during treatment was greater. The adjusted odds ratio for greater WLG among HPV-positive versus HPV-negative was 0.47 (95%CI 0.28-0.78). Grade-4 WLG (worst category) experienced poorer OS and CSS (OS adjusted hazard ratio (aHR) 4.08; 95%CI 1.48-11.2, compared to Grade-0); and was non-significant for HPV-negative (aHR 2.34; 95%CI 0.69-7.95). Relationships between weight change before/during treatment and survival had similar direction between HPV-positive and HPV-negative, but of greater magnitude in HPV-positive patients.

The collateral impact of the COVID-19 pandemic on HPV-positive oropharyngeal cancer diagnosis.

PURPOSE: We aim to assess the potential impact of the COVID-19 pandemic on diagnostic delays in HPV-positive oropharyngeal cancer (OPC), and to describe their underlying reasons. METHODS: All HPV + OPC referred to a tertiary cancer centre and diagnosed between June-December 2019 (Pre-Pandemic cohort) vs June-December 2020 (Pandemic cohort) were reviewed. TNM classification, gross-tumor-volumes (GTV) and intervals between sign/symptom onset and treatment initiation were compared between the cohorts. Reasons for delay (>6 months from onset of signs/symptoms to a positive biopsy of the primary tumor, or a delay specifically mentioned in the patient chart) in establishing the diagnosis were recorded per clinician's documentation, and categorized as COVID-related or non-COVID-related. RESULTS: A total of 157 consecutive HPV + OPC patients were identified (Pre-Pandemic: 92; Pandemic: 65). Compared to the Pre-Pandemic cohort, Pandemic cohort patients had a higher proportion of N2-N3 (32 % vs 15 %, p = 0.019) and stage III (38 % vs 23 %, p = 0.034) disease at presentation. The differences in proportions with > 6 months delay from symptom onset to establishing the diagnosis (29 % vs 20 %, p = 0.16) or to first treatment (49 % vs 38 %, p = 0.22) were not statistically different. 47 % of diagnostic delays in the Pandemic cohort were potentially attributable to COVID-19. CONCLUSION: We observed a collateral impact of the COVID-19 pandemic on HPV + OPC care through more advanced stage at presentation and a non-significant but numerically longer interval to diagnosis. This could adversely impact patient outcomes and future resource allocation. Both COVID-19-related and unrelated factors contribute to diagnostic delays. Tailored interventions to reduce delays are warranted.

Association of Primary Tumor Volume With Survival in Patients With T3 Glottic Cancer Treated With Radiotherapy: A Study of the Canadian Head & Neck Collaborative Research Initiative.

Importance: The association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors. Objective: To evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study. Design, Setting, and Participants: This multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018. Tumor volume was measured by expert neuroradiologists on diagnostic imaging. Clinical and outcome data were extracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) outcomes were assessed with marginal Cox regression. Laryngectomy-free survival (LFS) was modeled as a secondary analysis. Patients diagnosed with cT3 N0-N3 M0 glottic cancers from 2002 to 2018 and treated with curative intent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Overall, 319 patients met study inclusion criteria. Exposures: Tumor volume as measured on diagnostic imaging by expert neuroradiologists. Main Outcomes and Measures: Primary outcomes were OS and DFS; LFS was assessed as a secondary analysis, and late toxic effects as an exploratory analysis determined before start of the study. Results: The mean (SD) age of participants was 66 (12) years and 279 (88%) were men. Overall, 268 patients (84%) had N0 disease, and 150 (47%) received concurrent systemic therapy. The mean (SD) tumor volume was 4.04 (3.92) cm3. With a mean (SD) follow-up of 3.85 (3.04) years, there were 91 (29%) local, 35 (11%) regional, and 38 (12%) distant failures. Increasing tumor volume (per 1-cm3 increase) was associated with significantly worse adjusted OS (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11) and DFS (HR, 1.04; 95% CI, 1.01-1.07). A total of 62 patients (19%) underwent laryngectomies with 54 (87%) of these within 800 days after treatment. Concurrent systemic therapy was associated with improved LFS (subdistribution HR, 0.63; 95% CI, 0.53-0.76). Conclusions and Relevance: Increasing tumor volumes in cT3 glottic cancers was associated with worse OS and DFS, and systemic therapy was associated with improved LFS. In absence of randomized clinical trial evidence, patients with poor pretreatment laryngeal function or those ineligible for systemic therapy may be considered for primary surgical resection with postoperative radiotherapy.

Comparing unilateral vs. bilateral neck management in lateralized oropharyngeal cancer between surgical and radiation oncologists: An international practice pattern survey.

BACKGROUND: Management of the neck in oropharyngeal carcinoma varies due to a lack of clarity of patterns of lymphatic drainage and concern of failure in the contralateral neck. With recent advances in transoral surgical techniques, surgical management has become increasingly prevalent as the primary treatment modality. We compare international practice patterns between surgical and radiation oncologists. METHODS: A survey of neck management practice patterns was developed and pilot tested by 6 experts. The survey comprised items eliciting the nature of clinical practice, as well as patterns of neck management depending on extent of nodal disease and location and extent of primary site disease. Proportions of surgical and radiation oncologists treating the neck bilaterally were compared using the chi-squared statistic. RESULTS: Two-hundred and twenty-two responses were received from 172 surgical oncologists, 44 radiation oncologists, 3 medical oncologists, and 3 non-oncologists from 32 different countries. For tongue base cancers within 1 cm of midline (67% vs. 100%, p < 0.001), and for tonsil cancers with extension to the medial 1/3 of the soft palate (65% vs. 100%, p < 0.001) or tongue base (77% vs. 100%, p < 0.001), surgical oncologists were less likely to treat the neck bilaterally. For isolated tonsil fossa cancers with no nodal disease, both surgical and radiation oncologists were similarly likely to treat unilaterally (99% vs. 97%, p = NS). However, with increasing nodal burden, radiation oncologists were more likely to treat bilaterally for scenarios with a single node < 3 cm (15% vs. 2%, p < 0.001), a single node with extranodal extension (41% vs. 18%, p < 0.001), multiple positive nodes (55% vs. 23% p < 0.001), and node(s) > 6 cm (86% vs. 33%, p < 0.001). For tumors with midline extension, even with a negative PET in the contralateral neck, the majority of surgical and radiation oncologists would still treat the neck bilaterally (53% and 84% respectively). CONCLUSIONS: The present study demonstrates significant practice pattern variability for management of the neck in patients with lateralized oropharyngeal carcinoma. Surgical oncologists are less likely to treat the neck bilaterally, regardless of tumor location or nodal burden. Even in the absence of disease in the contralateral neck on imaging, them majority of practitioners are likely to treat bilaterally when the disease approaches midline.

Sexual satisfaction in nasopharyngeal carcinoma survivors: Rates and determinants.

OBJECTIVES: Sexual health problems have been identified as an unmet need in head and neck cancer (HNC) survivors. In particular, little is known about such outcomes in survivors of nasopharyngeal cancer (NPC). MATERIALS AND METHODS: A cross-sectional study of NPC survivors with ≥4y follow-up was undertaken. Sexual satisfaction was assessed using the optional "I am satisfied with my sex life" item of the FACT-H&N. Other patient-reported outcomes measures were also captured including fatigue (FACIT-F), HNC symptom burden (MDASI-HN), emotional distress (HADS) and frontal function (FrSBE). Univariate and multivariate analyses were performed to determine factors influencing sexual satisfaction. RESULTS: The sexual satisfaction item was answered by 85/103 (83%) enrollees. Female (p < 0.001) and non-partnered (p = 0.0045) patients were more likely to abstain from answering. The distribution of responses were: "very much" (26%), "quite a bit" (21%), "somewhat" (20%), "a little bit" (13%) and "not at all" (20%). Sexual satisfaction was associated with multiple patient-reported measures on univariate analysis, including quality of life, fatigue, a priori selected HNC symptoms (pain, taste), emotional distress, frontal lobe function, body image and relationship strength. On multivariate analysis, only relationship strength and emotional distress remained significant. Sociodemographic factors (age, sex, marital status) and other selected orofacial toxicities were not significant. CONCLUSIONS: Nearly half (47%) of our sample reported being in the higher satisfaction range. While reassuring in the context of comparative population level data, a number of factors including toxicity, psychological and social factors were associated with sexual satisfaction responses. Prospective evaluation of this unmet need is required.

Durable therapeutic gain despite competing mortality in long-term follow-up of a randomized hyperfractionated radiotherapy trial for locally advanced head and neck cancer.

PURPOSE/OBJECTIVES: To examine the therapeutic ratio and mortality profile over time in a radiotherapy randomized trial in stage III-IV larynx/pharynx cancer with long-term follow-up. MATERIALS/METHODS: From 1988 to 1995, 331 cases were randomized to either hyperfractionated (HF) (58 Gy/40 fractions, twice daily) or conventional (CF) (51 Gy/20 fractions, once daily) radiotherapy. Overall survival (OS), locoregional (LRC), distant control (DC), ≥Grade 3 late toxicity (LT), and relative mortality risk profile over time were compared between both arms. RESULTS: Median follow-up was 13.6 years. HF had a 10% improved OS at 5-years (40% vs 30%, p = 0.04), but the benefit diminished to 3% at 10-years (21% vs 18%). A trend towards higher LRC with HF remained (5-year: 49% vs 40%; 10-year: 49% vs 39%, p = 0.05). DC rates were unchanged (5-year: 87% vs 85%; 10-year: 87 vs 84%, p = 0.56). LT rates were similar (HF vs CF: 5-year: 9% vs 12%; 10-year: 11% vs 14%, p = 0.27). Multivariable analysis confirmed that HF reduced mortality risk by 31% [HR 0.69 (0.55-0.88), p < 0.01] and locoregional failure risk by 35% [HR 0.65 (0.48-0.89), p < 0.01]. Index cancer mortality (5-year: 46% vs 51%; 10-year: 49% vs 55%) was lower in the HF arm. Competing mortality (mostly smoking-related) was also numerically lower with HF at 5-years (14% vs 19%) but became similar at 10-years (30% vs 28%). CONCLUSIONS: This trial confirms that HF with augmented total dose has a durable 10% effect size on LRC with comparable LT. OS benefit is evident at 5-years (10%) but relative mortality risk profile changes in longer follow-up.

Depicting distant metastatic risk by refined subgroups derived from the 8th edition nasopharyngeal carcinoma TNM.

BACKGROUND: Tumor-nodal-metastasis (TNM) is the most important survival predictor in nasopharyngeal carcinoma (NPC). Distant metastasis (DM) is the predominant failure pattern of NPC in the intensity-modulated radiotherapy (IMRT) era. The DM risk appears to be different for T-N subsets within the same clinical stage. Appropriately depicting DM risk has emerged as an important issue in tailoring individualized treatment and underpins the reason for this study. METHODS: A total of 1616 non-metastatic (M0) NPC patients treated with IMRT were included. All were re-staged according to the 8th edition AJCC/UICC TNM (TNM-8). DM-free survival (DMFS) was calculated and compared among T-N subsets within each stage and DM risk groups were derived by Recursive-partitioning analysis (RPA) based on ordinal T and N categories. RESULTS: Significant heterogeneity in DM risk was evident among T-N subsets within cTNM-8 stages II-IV. The RPA algorithm classified patients into four DM risk groups: RPA-I (T1N0-1 and T2-3N0), RPA-II (T2-3N1), RPA-III (T4N0-1 and T1-3N2) and RPA-IV (T4N2 and T1-4N3), with 5-year DMFS of 93.4% (95% CI: 91.3-96.1), 84.3% (80.8-87.8), 78.9% (75.4-82.4) and 63.6% (56.3-70.9), respectively (p < 0.001). Compared to cTNM-8 stage grouping, RPA grouping had a lower Akaike information criterion (AIC) and higher Harrell's concordance index (c-index) for DMFS. CONCLUSIONS: Significant heterogeneity in DM risk exists among T-N subsets within cTNM-8 stages. The RPA groups demonstrated improved intra-group hazard consistency compared to cTNM-8 stage groups. While further validation is warranted, these RPA prognostic groupings provide a strong anatomic foundation to augment DM prediction for optimal targeting in future clinical trials.

Outcome following radiotherapy for head and neck basal cell carcinoma with 'aggressive' features.

OBJECTIVES: The literature demonstrates that 'aggressive' head-and-neck basal cell carcinomas (HN-BCC) have a higher than expected relapse rate with unfavorable outcomes. We report outcomes following definitive (dRT) or post-operative radiotherapy (PORT) for these tumors. METHODS: We reviewed all HN-BCC patients with 'aggressive' features (primary lesions diameter >10mm, >2 recurrences, or extra-cutaneous extension), treated with megavoltage dRT or PORT between 1998 and 2013. Loco-regional control (LRC) and relapse-free survival (RFS) were estimated using the competing risk method, and overall survival (OS) by Kaplan-Meier method. Univariable analysis explored factors associated with relapse. RESULTS: A total of 108 histologically confirmed 'aggressive' HN-BCC patients were identified, including 38 (35%) presenting de novo and 70 (65%) treated for recurrence (rBCC). dRT was offered to 72 (66.7%) patients and PORT to 36 (33.3%). Median follow-up was 3.5years. Actuarial 3-year LRC, RFS, and OS were 87% (95% confidence interval: 77-92), 82% (72-89), and 87% (80-94), respectively. LRC rates for dRT and PORT were similar [hazard ratio (HR) 0.61 (0.17-2.23), p=0.46]. Factors associated with higher risk of relapse were: rBCC [HR 7.96 (1.03-61.71), p=0.047], 'H-zone' (mid face, eyes, and ears) location [HR 3.13 (1.07-9.19), p=0.04], tumor size [HR 1.32 (1.08-1.6), p=0.006], nodal involvement [HR 3.68 (1.11-12.2), p=0.03] and stage [HR 3.13 (1.19-8.26), p=0.02]. CONCLUSION: RT is an effective treatment for 'aggressive' HN-BCC when used as a definitive modality or as PORT. Non-surgical management with definitive radiotherapy provides an alternative effective option if surgery is not used.