Disparities in clinical trial enrollment at a Canadian comprehensive cancer center: A 15-year retrospective study.

INTRODUCTION: Disparities in clinical trials (CTs) enrollment perpetuate inequities in treatment access and outcomes, but there is a paucity of Canadian data. The objective of this study was to examine disparities in cancer CT enrollment at a large Canadian comprehensive cancer center. METHODS: Retrospective study of CT enrollment among new patient consultations from 2006 to 2019, with follow-up to 2021 (N = 154,880), with the primary outcome of enrollment as a binary variable. Factors associated with CT enrollment were evaluated using multivariable Bayesian hierarchical logistic regression with random effects for most responsible physician (MRP) and geography, adjusted for patient characteristics (sex, age, language, geography, and primary care provider [PCP]), area-level marginalization (residential instability, material deprivation, dependency, and ethnic concentration), disease (cancer site and stage), and MRP (department, sex, language, and training). A sensitivity analysis of the cumulative incidence of enrollment was conducted to account for differences in disease type and follow-up length. RESULTS: CT enrollment was 11.2% overall, with a 15-year cumulative incidence of 18%. Lower odds of enrollment were observed in patients who were female (adjusted odds ratio [AOR], 0.82; 95% confidence interval [CI], 0.78-0.86), ≥65 years (AOR vs. <40, 0.61; 95% CI, 0.56-0.66), non-English speakers (0.72; 95% CI, 0.67-0.77), living ≥250 km away (AOR vs. <15 km, 0.71; 95% CI, 0.62-0.80), and without a PCP. Disease characteristics accounted for the largest proportion of observed variation (20.8%), with significantly greater odds of enrollment in patients with genitourinary cancers and late-stage disease. CONCLUSION: Significant sociodemographic disparities were observed, suggesting the need for targeted strategies to increase diversity in access to cancer CTs in Canada.

A dose escalation study of hyperfractionated accelerated radiation delivered with integrated neck surgery (HARDWINS) for the management of advanced head and neck cancer.

BACKGROUND AND PURPOSE: To determine toxicity and outcome of radiation dose escalation with hyperfractionated accelerated radiation delivered with neck surgery (HARDWINS) for head and neck cancer. PATIENTS AND METHODS: Patients with stage III and IV squamous cell carcinoma of the oropharynx, hypopharynx or larynx were enrolled. Dose levels of 60, 62 and 64Gy were delivered with twice daily fractionation in 40 fractions over 4 weeks. Involved and at-risk nodal regions received microscopic dose (46.5-48Gy) with neck dissection for node positive patients 8 weeks after radiation. RESULTS: One hundred and sixty-nine patients were enrolled (60Gy n=22, 62Gy n=26, 64Gy n=121). No grade 4 acute toxicity was observed. Incidence of acute grade 3 toxicity was: skin (2%), larynx (6%), pharynx and esophagus (66%) and mucous membrane (75%). Feeding tube dependence was observed in 14% of patients receiving 64Gy. Overall survival, and relapse free rate at 5 years were 65% and 63%, respectively. Local, nodal and distant relapse free rates at 5 years were 77%, 94% and 81% (median follow-up 3.8 years). CONCLUSIONS: HARDWINS can be delivered without acute grade 4 toxicity but significant grade 3 acute toxicity. A significant proportion of the patients have prolonged swallowing dysfunction. Outcomes suggest this regimen represents an alternative to chemoradiation.

Hyperfractionated, accelerated radiotherapy for locally advanced head and neck cancer: quality of life in a prospective phase I/II trial.

BACKGROUND AND PURPOSE: Quality of life (QOL) was measured prospectively in a dose escalation study of twice daily hyperfractionated, accelerated radiotherapy for locally advanced head and neck cancer (HNC). MATERIALS AND METHODS: Patients with squamous cell HNC (TNM stage III/IV larynx or pharynx, or hypopharynx any stage) received 40 fractions of twice daily RT at 3 dose levels: (L1) 60Gy, 1.5Gy/fraction; (L2) 62Gy, 1.55Gy/fraction; and (L3) 64Gy, 1.6Gy/fraction. QOL was measured on the FACT-H&N at baseline, 6 and 12 months. RESULTS: Mean QOL scores were: baseline 104, 6 months 108, 12 months 112. At all time points, QOL scores were lower in patients with more advanced T-category. A mixed-model analysis of determinants of QOL showed no dose effect among L1 (n=22), L2 (n=26) or L3 (n=123). QOL improved significantly with time from diagnosis, however post-treatment QOL was lower and improved more slowly in patients who had feeding tubes. CONCLUSIONS: Post-RT QOL improved from baseline by a statistically and clinically significant amount. Hyperfractionated, accelerated RT provides favorable QOL outcomes, and is a viable alternative to chemoradiation for patients with locally advanced HNC.

Limitation of conventional two dimensional radiation therapy planning in nasopharyngeal carcinoma.

PURPOSE: To assess the adequacy of coverage of gross tumor volume (GTV) with traditional two dimensional (2D) radiation therapy (RT) planning in patients with nasopharyngeal cancer (NPC). MATERIALS AND METHODS: The study comprised 94 of 179 patients treated with definitive RT between 1993 and 1997. The inclusion requirement was the availability of a digitally archived pretreatment magnetic resonance imaging. The digital images were used to record the precise location of the GTV in the sagittal plane. As a separate procedure, sagittal dose distributions for each treatment phase were created by digitizing the simulation field parameters into treatment planning software without knowledge of the GTV. The location of the GTV and dose distribution in the sagittal plane were superimposed on each other and GTV coverage by the 50, 90 and 95% isodose lines determined for each phase of treatment. RESULTS: The 1997 tumour node metastasis (TNM) stage distribution was: 7 (8%) stage I, 16 (16%) stage II, 30 (32%) stage III and 41 (44%) stage IV. Median follow-up was 4.4 years. Median primary dose was 66 Gy. The actuarial 5-year overall survival, disease free survival and local relapse free rates were 88, 54 and 66%, respectively. The GTV was covered by the 50, 90 and 95% isodose lines for all phases of the multiphase plan in only 53, 20 and 9% of patients, respectively. The GTV was more likely to be undercovered in the latter phases of the plan particularly in those patients with advanced T category. CONCLUSION: 2D RT planning has significant limitations in achieving adequate GTV coverage in NPC. We strongly recommend 3D planning using either conformal techniques of dose delivery or intensity modulated radiation therapy for the treatment of these patients.

Preoperative radiotherapy for adult head and neck soft tissue sarcoma: assessment of wound complication rates and cancer outcome in a prospective series.

Combination surgery and radiotherapy (RT) is frequently used in soft tissue sarcoma (STS). Because lower doses and smaller irradiation volumes are possible in preoperative RT (pre-op RT), this approach can be especially valuable in anatomic settings where critical organs are in close proximity to the RT target area. A recent multicenter phase III trial (SR.2 trial of the National Cancer Institute of Canada Clinical Trials Group) comparing pre-op RT against post-op RT for extremity STS has shown significantly higher major wound complication rates (35%) with pre-op RT. We postulated that wound complication rates may be less frequent in the head and neck with better vascularity and wider use of secondary wound reconstruction. Using a prospective database, we identified 40 consecutive patients with head and neck STS treated with pre-op RT (50 Gy) and subsequent (4 to 6 weeks later) resection between 1/89 and 8/99 in a single institution setting. Major wound complications (MWC) were classified by the identical criteria used in the SR.2 trial. Intracranial extension was evident in 5 patients, whereas 50% of the patients had large tumors (> 5 cm). Deep tumor was present in 34 (85%), and 6 (15%) were superficial to fascia. In this series, 31 patients (77.5%) had secondary reconstruction of the acquired soft tissue deficit. The actuarial 2-year local relapse-free rate was 80%, and the metastatic relapse-free rate was 85%. Major wound complications occurred in 8 of 40 patients (20%) within 120 days of surgery according to the SR.2 criteria: secondary wound surgery (3), readmission or prolonged hospital admission for wound care (2), deep packing (0), prolonged dressing changes (2), and invasive procedure for wound care (1). The latter was a minor wound management problem (a single outpatient drainage of a seroma) for the combined rate of 8/20 or 20%. Our findings show that (1) pre-op RT in head and neck STS is associated with lower rates of major wound complications compared to extremity cases; (2) pre-op RT provides high rates of local control in an adverse group of cases of adult head and neck STS; (3) the choice of scheduling of RT should be based on anatomic issues with emphasis on the trade-offs between RT doses and volumes versus wound morbidity for individual patients. This is especially important when tumor may be adjacent to critical head and neck structures which may be protected from the high-dose RT area.