Radiology-Pathology Concordance and Prognostication of Nodal Features in pN+ Oral Cavity Cancer.

BACKGROUND AND PURPOSE: The aims of our study are to evaluate the diagnostic performance and prognostic value of radiological lymph node (LN) characteristics in pN+ oral cavity squamous carcinoma (OSCC). MATERIALS AND METHODS: pN+ OSCC treated between 2012 and 2020 were included. Preoperative imaging was reviewed by a single radiologist blinded to pathologic findings for the following nodal features: imaging-positive LN (iN+), laterality and total number, and image-identified extranodal extension (iENE). The sensitivity of iN+ for pN+ was calculated. The diagnostic performance of other nodal features was evaluated in the iN+ subgroup. The association of radiologic nodal features with overall survival (OS) was evaluated. Inter-rater kappa for radiologic nodal features was assessed in 100 randomly selected cases. RESULTS: Of 406 pN+ OSCC, 288 were iN+. The sensitivity of iN+ for pN+ was 71% overall, and improved to 89% for pN+ LN >1.5 cm. Within iN+, sensitivity/specificity for LN size (>3 cm), total LN number (>4), and ENE were 0.44/0.95, 0.57/0.84, and 0.27/0.96, respectively. Sensitivity of iENE was higher in the subset, with major (>2 mm) versus minor (≤2 mm) pENE (43% vs. 13%, p = 0.001). Reduced OS was observed in iN+ versus iN- (p = 0.006), iENE+ versus iENE- (p = 0.004), LN size >3 versus ≤3 cm (p < 0.001), and higher LN number (p < 0.001). Inter-rater kappa for iN+, laterality, total LN number, and presence of iENE were 0.71, 0.57, 0.78, and 0.69, respectively. CONCLUSION: Our study shows that despite modest sensitivity of most radiological nodal features, the specificity of image-identified nodal features is high and their prognostic values are retained in pN+ OSCC. LEVEL OF EVIDENCE: Level 3 (retrospective review comparing cases and controls) Laryngoscope, 2024.

A Hard Truth to Swallow: Critically Evaluating the MD Anderson Dysphagia Inventory (MDADI) as an Endpoint in Human Papillomavirus-associated Oropharyngeal Cancer Trials.

The MD Anderson Dysphagia Inventory (MDADI), a measure of swallowing-related quality of life, has become the preferred patient-reported outcome measure (PROM) in contemporary clinical trials evaluating the experience of human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC) survivors. With many potentially practice-changing studies using the MDADI composite score as either a primary or coprimary endpoint, or as a key secondary endpoint, it is important to understand its psychometric properties as judged by contemporary PROM standards, with a particular focus on its application to contemporary HPVOPSCC populations. In this critical review, we evaluate contemporary HPVOPSCC studies reporting MDADI outcomes, followed by a detailed evaluation of the psychometric properties of the MDADI. Although the focus of this review was the MDADI, the issues discussed are not unique to the MDADI and have broader applicability to the evaluation and assessment of other PROMs currently in use. First, it may be possible to improve administration of the instrument, as related to missing items, scoring, and the number of items required. Second, although in many instances, the MDADI has been intended as a direct or surrogate measure of swallowing physiology, the MDADI composite score captures a broader health-related quality of life construct affected by both swallowing and eating, the latter of which may be affected by a range of nonswallowing treatment-related toxicities. Finally, a clinically meaningful change of 10 in the MDADI composite score, widely accepted and applied to the clinical trial setting, represents an undoubtably clinically relevant difference in unselected head and neck cancer survivors. However, the smallest difference that might be clinically important to a highly functional HPVOPSCC cohort remains uncertain. Understanding the purpose and properties of the MDADI instrument and furthering the sophistication with which we apply it in this population would improve its interpretation in clinical trials.

Telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER): A pilot study for patients treated with surgery for oral cavity carcinoma.

BACKGROUND: To address the rehabilitative barriers to frequency and precision of care, we conducted a pilot study of a biofeedback electropalatography (EPG) device paired with telemedicine for patients who underwent primary surgery +/- adjuvant radiation for oral cavity carcinoma. We hypothesized that lingual optimization followed by telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER) would further improve speech and swallowing outcomes after "standard-of-care" SOC rehabilitation. METHOD: Pilot prospective 8-week (TEBER) program following 8 weeks of (SOC) rehabilitation. RESULTS: Twenty-seven patients were included and 11 completed the protocol. When examining the benefit of TEBER independent of standard of care, "range-of-liquids" improved by +0.36 [95% CI, 0.02-0.70, p = 0.05] and "range-of-solids" improved by +0.73 [95% CI, 0.12-1.34, p = 0.03]. There was a positive trend toward better oral cavity obliteration; residual volume decreased by -1.2 [95% CI, -2.45 to 0.053, p = 0.06], and "nutritional-mode" increased by +0.55 [95% CI, -0.15 to 1.24, p = 0.08]. CONCLUSION: This pilot suggests that TEBER bolsters oral rehabilitation after 8 weeks of SOC lingual range of motion.

Evaluation of a National Radiation Oncology Research and Mentorship Program.

PURPOSE: The Canadian Association of Radiation Oncology Annual Scientific Meeting Medical Student Research and Mentorship Award was established in 2020 to support medical students pursuing radiation oncology (RO) research and RO as a career. This study is an evaluation of the effect of this national research and mentorship award on medical students, resident mentors, and research supervisors over 3 iterations. METHODS AND MATERIALS: Three separate surveys were created for medical student mentees, RO resident mentors, and attending research supervisors. These surveys were developed using best practice strategies for medical education surveys and circulated for peer review among experts in oncology medical education. The surveys were sent to the 52 individuals (18 students, 18 residents, 16 supervisors) who participated in 3 cycles of Canadian Association of Radiation Oncology ASM MSRMA (2020-21, 2021-22, 2022-23). After anonymization, quantitative answers were analyzed using descriptive statistics, and narrative responses were evaluated using a grounded theory approach. RESULTS: There was a 90% survey response rate. For medical student mentees, the award maintained (71%) or increased (24%) interest in pursuing an RO career. Students reported receiving helpful tips for residency applications and insight into RO residency, research, and career planning advice. Only the first student cohort currently has matching results for residency, with approximately 50% matching to RO. All resident mentor respondents felt the program either maintained or increased motivation to mentor students in RO. Research project supervisors unanimously enjoyed their role in this program and would recommend and participate in this program again. CONCLUSIONS: A national research and mentorship award for medical students has shown a positive effect on participants. Medical students felt this award program motivated them to continue pursuing oncology research and a potential career in RO. The program also enhanced mentorship skills in residents and research supervisors, which encourages further RO mentorship, teaching, and exposure for future generations of students.

Causes and impact of delays during the COVID-19 pandemic on head and neck cancer diagnosis.

BACKGROUND: The causes for delays during the COVID19 pandemic and their impact on head and neck cancer (HNC) diagnosis and staging are not well described. METHODS: Two cohorts were defined a priori for review and analysis-a Pre-Pandemic cohort (June 1 to December 31, 2019) and a Pandemic cohort (June 1 to December 31, 2020). Delays were categorized as COVID-19 related or not, and as clinician, patient, or policy related. RESULTS: A total of 638 HNC patients were identified including 327 in the Pre-Pandemic Cohort and 311 in the Pandemic Cohort. Patients in the Pandemic cohort had more N2-N3 category (41% vs. 33%, p = 0.03), T3-T4 category (63% vs. 50%, p = 0.002), and stage III-IV (71% vs. 58%, p < 0.001) disease. Several intervals in the diagnosis to treatment pathway were significantly longer in the pandemic cohort as compared to the Pre-Pandemic cohort. Among the pandemic cohort, 146 (47%) experienced a delay, with 112 related to the COVID-19 pandemic; 80 (71%) were clinician related, 15 (13%) were patient related, and 17 (15%) were policy related. CONCLUSIONS: Patients in the Pandemic cohort had higher stage disease at diagnosis and longer intervals along the diagnostic pathway, with COVID-19 related clinician factors being the most common cause of delay.

Patient-reported outcome measures for dysphagia in head and neck cancer: A systematic review and appraisal of content validity and internal structure.

Dysphagia is a major head and neck cancer (HNC) issue. Dysphagia-related patient-reported outcome measures (PROMs) are critical for patient-centred assessment and intervention tailoring. This systematic review aimed to derive a comprehensive inventory of HNC dysphagia PROMs and appraise their content validity and internal structure. Six electronic databases were searched to February 2023 for studies detailing PROM content validity or internal structure. Eligible PROMs were those developed or validated for HNC, with ≥20% of items related to swallowing. Two independent raters screened citations and full-text articles. Critical appraisal followed COSMIN guidelines. Overall, 114 studies were included, yielding 39 PROMs (17 dysphagia-specific and 22 generic). Of included studies, 33 addressed PROM content validity and 78 internal structure. Of all PROMs, only the SOAL met COSMIN standards for both sufficient content validity and internal structure. Notably, the development of 18 PROMs predated the publication of COSMIN standards. In conclusion, this review identified 39 PROMs addressing dysphagia in HNC, of which only one met COSMIN quality criteria. Given that half of PROMs were developed prior to COSMIN guidelines, future application of current standards is needed to establish their psychometric quality.

A core outcome set for patient-reported dysphagia for use in head and neck cancer clinical trials: An international multistakeholder Delphi study.

BACKGROUND: Measuring dysphagia-related patient-reported outcomes (PROs) in Head and Neck Cancer (HNC) patients is challenging due to dysphagia's multidimensional impact, causing inconsistency in outcome reporting. To address this issue, this study derived a consensus-based core outcome set (COS) for patient-reported dysphagia in HNC clinical trials where swallowing is a primary or secondary endpoint. METHODS: A sample of HNC clinicians, researchers, patients, and caregivers participated in a 2-Round Delphi technique. A Delphi survey, containing a comprehensive list of dysphagia-related PROs, was developed. In Round 1, participants rated item importance on a 5-point scale. Items rated ≥4 by >70% advanced to Round 2, where a consensus meeting addressed items with varied opinions, and the Delphi survey with remaining items was completed. Items rated ≥4 by >70% formed the final COS. RESULTS: Forty-five participants from nine countries were recruited. After Round 1, 40 items were excluded and 64 advanced to Round 2. After Round 2, a 7-outcome COS was established, comprising the domains of dysphagia symptoms, health status and quality of life. CONCLUSION: This study achieved consensus among HNC stakeholders on essential dysphagia PROs for HNC clinical trials. It is advisable to include these 7-core concepts in clinical trials involving people with HNC to facilitate treatment comparisons and data synthesis.

Efficacy of the Rehabilitation Planning Consult for Survivors of Head and Neck Cancer: A Phase 2 Randomized Controlled Trial.

PURPOSE: Survivors of head and neck cancer may have significant lasting impairments and poor access to rehabilitation. To address this, our group developed and evaluated a rehabilitation planning consult (RPC). The RPC is conducted through an initial consultation and a single follow-up session with a rehabilitation professional. During the initial consultation, rehabilitation needs are determined and the survivor sets individualized goals and plans. They then implement their plans independently and are facilitated to evaluate and modify plans as necessary during the follow-up session. METHODS AND MATERIALS: We used a waitlist control design to compare the proportion of participants attaining a minimally importantly different change in quality of life (QOL) on the Short Form 36 Physical Health Summary Score from baseline to 3 months after study enrollment, between patients randomized to receive (n = 77) or wait 14 ± 3 weeks to receive (n = 76) the RPC. Additional outcomes included goal attainment indicators measured using the Brief Rehabilitation Assessment for Survivors of Head and Neck Cancer (BRASH). RESULTS: Of 153 participants recruited, 95 (62%) completed the intervention; 57 were in the immediate (RPC) group and 38 were in the waiting list control (WLC) group. No significant between-group differences were seen in the proportion of patients achieving a minimally important improvement (2.5 units) on the Physical Health Summary Score from baseline to 3 months after recruitment. No between-group differences were seen on any secondary QOL indicators. Among the 67 (RPC n = 42, WLC n = 22) participants who set individualized rehabilitation goals, BRASH scores on goal performance and satisfaction with goal performance were significantly better in the RPC group. CONCLUSIONS: Our results suggest that the RPC may provide benefit in patients' individualized domains of choice among those who set goals, without affecting overall QOL. Future work could refine the subset of patients who benefit and explore the optimal timing and intensity of the intervention.

The Acceptability of Behavioural Swallowing Interventions for Head and Neck Cancer Patients During Radiotherapy: A Qualitative Study Exploring Experiences of Clinical Trial Speech-Language Pathologists.

The PRO-ACTIVE randomized clinical trial offers 3 swallowing therapies to Head and Neck Cancer (HNC) patients during radiotherapy (RT) namely: reactive, proactive low- ("EAT-RT" only) and high-intensity ("EAT-RT + exercises"). Understanding the experiences of the trial Speech-Language Pathologists (SLPs) will be useful to inform clinical implementation. This study assessed SLP opinions of acceptability and clinical feasibility of the 3 trial therapies. 8 SLPs from 3 Canadian PRO-ACTIVE trial sites participated in individual interviews. Using a qualitative approach, data collection and thematic analysis were guided by the Theoretical Framework of Acceptability. Member checking was conducted through a follow-up focus group with willing participants. Seven themes were derived: intervention coherence, burden, barriers/facilitators, self-efficacy, attitude, ethicality, and perceived effectiveness. SLPs felt all 3 therapies had potential benefit yet perceived more advantages of proactive therapies compared to reactive. Compared to exercises, SLPs particularly endorsed the EAT-RT component. A major barrier was keeping patients motivated, which was impacted by acute toxicity and sometimes conflicting instructions from the healthcare team. Strategies utilized by to overcome barriers included: scaling exercises and/or diet up/down according to the changing patient needs and communicating therapy goals with healthcare team. A model was derived describing the perceived acceptability of the swallowing therapies according to SLPs, based on the interconnection of main themes. Proactive therapies were perceived as more acceptable to trial SLPs, for facilitating patient engagement. The perceived acceptability of the swallowing therapies was related to seven interconnected aspects of providers' experience. These findings will inform the implementation and potential uptake of the PRO-ACTIVE swallowing therapies in clinical practice.

Exploring the Acceptability of Behavioral Swallowing Interventions for Head and Neck Cancer Patients During Radiotherapy: A Qualitative Study of Patients' Experience.

The PRO-ACTIVE randomized clinical trial offers 3 swallowing therapies to Head and Neck Cancer (HNC) patients during radiotherapy namely: reactive, proactive low- ("EAT-RT" only), and high-intensity ("EAT-RT + exercises"). Understanding the perceived acceptability of these interventions is important to inform eventual implementation into clinical practice. This study explored patients' perspectives using qualitative methodology. At 2 Canadian PRO-ACTIVE trial sites, 24 trial participants were recruited for individual semi-structured interviews, representing each of the 3 trial arms. Data collection and thematic analysis were guided by the Theoretical Framework of Acceptability (TFA). Member checking was conducted through follow-up focus groups. Seven themes were derived reflecting the TFA constructs. Overall, regardless of trial arm, patients reported a positive experience with therapy. Patients identified benefits of EAT-RT therapy, reporting that it provided meaningful feedback on diet progress and supported goal setting for oral intake. Patients who received proactive therapies valued the opportunity to set expectations early, build mealtime routine iteratively over time, and have an extended engagement with the SLP. Regardless of trial arm, patients agreed proactive therapy aligned with what they think is best and that therapy intensity should accommodate individual needs. This study identified the value to HNC patients of receiving swallowing interventions during RT and setting realistic expectations around swallowing. Compared to reactive care, proactive therapies were perceived helpful in consolidating habits early, establishing realistic expectations around swallowing and building an extended rapport with the SLP. These findings will inform the implementation of proactive versus reactive swallowing therapies in clinical practice.

Supply and Demand for Radiation Oncologists in Canada: Workforce Planning Projections From 2020 to 2040.

PURPOSE: The number of Canadians diagnosed with cancer, and subsequent demand for radiation therapy, are expected to increase over time. This study aimed to update our needs-based workforce planning model to ensure appropriate staffing levels in the future. METHODS AND MATERIALS: The supply of radiation oncologists, by age group, sex, and full-time equivalent status, was projected from 2020 to 2040 using a recursive-aging, input-output model developed with seeding parameters derived from national sources. The demand for radiation oncologists until 2040 was estimated using referral patterns for radiation therapy and consultation workload metrics applied to projected annual cancer incident cases to calculate required full-time equivalent positions. Baseline model parameters were also applied to the 2005-2019 workforce and incident case data to evaluate preprojection supply and demand trends. RESULTS: Preprojection trends for 2005 to 2019 revealed accelerated staffing growth that transitioned from a workforce shortage to a surplus state in 2014 followed by substantial growth slowdown in 2016. The model predicts a transient surplus of radiation oncologists until 2026 followed by a projected deficit in subsequent years. Sensitivity analyses using the plausible range for each parameter continued to favor an undersupply, suggesting a trainee shortage unable to meet workforce expansion needs. Considering possible future declining trends in radiotherapy utilization and workload, calculations to inform corrective efforts in resident numbers resulted in 25 entry positions per year, up from 21 per year currently. Geographic distribution of trainees, relative to workforce and cancer incidence distributions, could be improved with more residency positions in Canadian regions outside Ontario. CONCLUSIONS: Demand for radiation therapy and radiation oncologists in Canada are expected to grow more quickly than future expansion in staffing levels. Our workforce planning model provides evidence for more trainee requirements to inform stakeholders of possible corrective actions to training programs and recruitment. Further research is needed to explore additional strategies to expand capacity and high-quality delivery of radiation therapy to meet the foreseeable increase in Canadian patients with cancer.

Implication of dental insurance status on patterns of pre-radiation dental extraction and risk of osteoradionecrosis of the jaw in head-and-neck cancer patients.

Oral toxicities such as osteoradionecrosis can be minimized by dental screening and prophylactic dental care prior to head and neck (HN) radiation therapy (RT). However, limited information is available about how dental insurance interacts with prophylactic dental care and osteoradionecrosis. To address this gap in knowledge, we conducted a cohort study of 2743 consecutive adult patients treated with curative radiation for HN malignancy who underwent pre-radiation dental assessment and where required, prophylactic dental treatment. Charts were reviewed to determine patient demographics, dental findings, dental treatment and development of osteoradionecrosis following radiation. Three insurance cohorts were identified: private-insured (50.4 %), public-insured (7.3 %), being patients with coverage through government-funded disability and welfare programs, and self-pay (42.4 %). More than half the public-insured patients underwent prophylactic pre-radiation dental extractions, followed by self-pay patients (44 %) and private-insured patients (26.6 %). After a median follow-up time of 4.23 years, 6.5 % of patients developed osteoradionecrosis. The actuarial rate of osteoradionecrosis in the public-insured patients was 14.7 % at 5-years post-RT, compared to 7.5 % in private-insured patients and 6.7 % in self-pay patients. On multivariable analysis, dental insurance status, DMFS160, age at diagnosis, sex, tumor site, nodal involvement, years smoked and gross income were all significant risk factors for tooth removal prior to HN radiation. However, only public-insured status, tumor site and years smoked were significant risk factors for development of osteoradionecrosis. Our findings demonstrate that lack of comprehensive dental coverage (patients who self-pay or who have limited coverage under public-insured programs) associates strongly with having teeth removed prior to HN RT. Nearly 1 in 6 patients covered under public-insurance developed osteoradionecrosis within 5 years of completing their treatment. Well-funded dental insurance programs for HN cancer patients might reduce the number of pre-RT extractions performed in these patients, improving quality of life post-RT.

Individualized risk assessment of distant metastases in oral cavity carcinoma: a validated predictive-score model.

BACKGROUND: We aimed to develop and validate a risk-scoring system for distant metastases (DMs) in oral cavity carcinoma (OCC). METHODS: Patients with OCC who were treated at 4 tertiary cancer institutions with curative surgery with or without postoperative radiation/chemoradiation therapy were randomly assigned to discovery or validation cohorts (3:2 ratio). Cases were staged on the basis of tumor, node, and metastasis staging according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control guidelines. Predictors of DMs on multivariable analysis in the discovery cohort were used to develop a risk-score model and classify patients into risk groups. The utility of the risk classification was evaluated in the validation cohort. RESULTS: Overall, 2749 patients were analyzed. Predictors (risk score coefficient) of DMs in the discovery cohort were the following: pathological stage (p)T3-4 (0.4), pN+ (N1: 0.8; N2: 1.0; N3: 1.5), histologic grade (G) 3 (G3, 0.7), and lymphovascular invasion (0.4). The DM risk groups were defined by the sum of the following risk score coefficients: high (>1.7), intermediate (0.7-1.7), and standard risk (<0.7). The 5-year DM rates (high/intermediate/standard risk groups) were 30%/15%/4% in the discovery cohort (C-index = 0.79) and 35%/16%/5% in the validation cohort, respectively (C-index = 0.77; both P < .001). In the whole cohort, this predictive model showed excellent discriminative ability in predicting DMs without locoregional failure (29%/11%/1%), later (>2 year) DMs (11%/4%/2%), and DMs in patients treated with surgery (20%/12%/5%), postoperative radiation therapy (34%/17%/4%), and postoperative chemoradiation therapy (39%/18%/7%) (all P < .001). The 5-year overall survival rates in the overall cohort were 25%/51%/67% (P < .001). CONCLUSIONS: Patients at higher risk for DMs were identified by use of a predictive-score model for DMs that included pT3-4, pN1/2/3, G3, and lymphovascular invasion. Identified patients may be evaluated for individualized risk-adaptive treatment escalation and/or surveillance strategies.

The Feasibility of Quality Assurance in the TOPGEAR International Phase 3 Clinical Trial of Neoadjuvant Chemoradiation Therapy for Gastric Cancer (an Intergroup Trial of the AGITG/TROG/NHMRC CTC/EORTC/CCTG).

PURPOSE: The TOPGEAR phase 3 trial hypothesized that adding preoperative chemoradiation therapy (CRT) to perioperative chemotherapy will improve survival in patients with gastric cancer. Owing to the complexity of gastric irradiation, a comprehensive radiation therapy quality assurance (RTQA) program was implemented. Our objective is to describe the RTQA methods and outcomes. METHODS AND MATERIALS: RTQA was undertaken in real time before treatment for the first 5 patients randomized to CRT from each center. Once acceptable quality was achieved, RTQA was completed for one-third of subsequent cases. RTQA consisted of evaluating (1) clinical target volume and organ-at-risk contouring and (2) radiation therapy planning parameters. Protocol violations between high- (20+ patients enrolled) and low-volume centers were compared using the Fisher exact test. RESULTS: TOPGEAR enrolled 574 patients, of whom 286 were randomized to receive preoperative CRT and 203 (71%) were included for RTQA. Of these, 67 (33%) and 136 (67%) patients were from high- and low-volume centers, respectively. The initial RTQA pass rate was 72%. In total, 28% of cases required resubmission. In total, 200 of 203 cases (99%) passed RTQA before treatment. Cases from low-volume centers required resubmission more often (44/136 [33%] vs 13/67 [18%]; P = .078). There was no change in the proportion of cases requiring resubmission over time. Most cases requiring resubmission had multiple protocol violations. At least 1 aspect of the clinical target volume had to be adjusted in all cases. Inadequate coverage of the duodenum was most common (53% major violation, 25% minor violation). For the remaining cases, the resubmission process was triggered secondary to poor contour/plan quality. CONCLUSIONS: In a large multicenter trial, RTQA is feasible and effective in achieving high-quality treatment plans. Ongoing education should be performed to ensure consistent quality during the entire study period.

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.

Health-related quality of life in early-stage Hodgkin lymphoma: a longitudinal analysis of the ABVD arm in the randomized controlled trial HD.6.

Early-stage Hodgkin lymphoma has become one of the most curable hematologic malignancies. Depending upon the disease location, possible toxicities, and patient preference, chemotherapy alone with ABVD remains an accepted treatment modality for this disease. There remains a paucity of data regarding the longitudinal trajectory of health-related quality of life (HRQoL) in patients treated for HL. The impact of disease and treatment on HRQoL is increasingly important to understand as the number of long-term survivors increases. We report the longitudinal HRQoL using data prospectively collected from diagnosis up to 10 years post-treatment in the ABVD arm of the HD.6 randomized controlled trial for early-stage HL patients (N=169). We analyzed HRQoL using the EORTC QLQ-C30 collected at baseline, 3 months, 6 months, and 12 months after completion of chemotherapy and yearly up to year 10. Clinically and statistically significant improvements were noted for specific domains including emotional (3 months post-treatment), social (12 months post-treatment) and financial functioning (2 years post-treatment), and the specific symptom of fatigue (6 months post-treatment) during the follow-up period. To our knowledge, this is the first prospective, longitudinal analysis of HRQoL specifically among patients with early-stage HL treated with ABVD therapy alone. Although improvements were noted, sustained clinically and statistically significant improvements were noted only in select symptoms emphasizing the need to better understand and optimize HRQoL among this patient group.

Effect of Radiation Therapy Quality Assurance on Nasopharyngeal Carcinoma: Usage of a Novel, Web-Based Quality Assurance Application.

PURPOSE: We used a new web application for rapid review of radiation therapy (RT) target volumes to evaluate the relationship between target delineation compliance with the international guidelines and outcomes of definitive RT for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The data set consisted of computed tomography simulation scans, RT structures, and clinical data of 354 patients with pathology-confirmed NPC treated with intensity modulated RT between 2005 and 2017. Target volumes were peer-reviewed in RT quality assurance rounds, and target contours were revised, if recommended, before treatment. We imported the contours of intermediate-risk clinical target volumes of the primary tumor (CTVp) of 332 patients into the application. Inclusion of anatomic sites within intermediate-risk CTVp was determined in accordance with 2018 international guidelines for CTV delineation for NPC and correlated with time to local failure (TTLF) using Cox regression. RESULTS: In the peer-review quality assurance analysis, local and distant control and overall survival rates were similar between peer-reviewed and nonreviewed cases and between cases with and without target contour changes. In the CTV compliance analysis, with a median follow-up of 5.6 years, 5-year TTLF and overall survival rates were 93.1% and 85.9%, respectively. The most frequently non-guideline-compliant anatomic sites were sphenoid sinus (n = 69, 20.8%), followed by cavernous sinus (n = 38, 19.3%), left and right petrous apices (n = 37 and 32, 11.1% and 9.6%), and clivus (n = 14, 4.2%). Among 23 patients with a local failure (6.9%), the number of noncompliant cases was 8 for sphenoid sinus, 7 cavernous sinus, 4 left and 3 right petrous apices, and 2 clivus. Cavernous sinus-conforming cases showed higher TTLF in comparison with nonconforming cases (93.6% vs 89.1%, P = .013). Multivariable analysis confirmed that cavernous sinus noncompliance was prognostic for TTLF. CONCLUSIONS: Our application allowed rapid quantitative review of CTVp in a large NPC cohort. Although compliance with the international guidelines was high, undercoverage of the cavernous sinus was correlated with TTLF.

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.

Evaluation of dosimetric predictors of toxicity after IMRT with concurrent chemotherapy for anal cancer.

BACKGROUND: This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy. MATERIALS AND METHODS: Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 1&5). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea). RESULTS: In total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder D0.5cc; G2 + inguino-genital skin toxicity and anterior skin V35; G2 + perianal skin toxicity and posterior skin V15; G2 + anemia and lower pelvis bone V45. D0.5 cc was significantly predictive of late toxicity (G2 + anal dysfunction, intestinal toxicity, and inguino-genital/perianal dermatitis). Maximum skin toxicity grade was significantly correlated with the requirement for a treatment break. CONCLUSION: Statistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.