Stereotactic Radiation Therapy in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease: A Nonrandomized Clinical Trial.

Importance: Patients with interstitial lung disease (ILD) and early-stage non-small cell lung cancer (NSCLC) have been reported to be at high risk of toxic effects after stereotactic ablative radiotherapy (SABR), but for many patients, there are limited alternative treatment options. Objective: To prospectively assess the benefits and toxic effects of SABR in this patient population. Design, Setting, and Participants: This prospective cohort study was conducted at 6 academic radiation oncology institutions, 5 in Canada and 1 in Scotland, with accrual between March 7, 2019, and January 12, 2022. Patients aged 18 years or older with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgical resection were enrolled. Intervention: Patients were treated with SABR to a dose of 50 Gy in 5 fractions every other day. Main Outcomes and Measures: The study prespecified that SABR would be considered worthwhile if median overall survival-the primary end point-was longer than 1 year, with a grade 3 to 4 risk of toxic effects less than 35% and a grade 5 risk of toxic effects less than 15%. Secondary end points included toxic effects, progression-free survival (PFS), local control (LC), quality-of-life outcomes, and changes in pulmonary function. Intention-to-treat analysis was conducted. Results: Thirty-nine patients enrolled and received SABR. Median age was 78 (IQR, 67-83) years and 59% (n = 23) were male. At baseline, 70% (26 of 37) of patients reported dyspnea, median forced expiratory volume in first second of expiration was 80% (IQR, 66%-90%) predicted, median forced vital capacity was 84% (IQR, 69%-94%) predicted, and median diffusion capacity of the lung for carbon monoxide was 49% (IQR, 38%-61%) predicted. Median follow-up was 19 (IQR, 14-25) months. Overall survival at 1 year was 79% (95%, CI 62%-89%; P < .001 vs the unacceptable rate), and median overall survival was 25 months (95% CI, 14 months to not reached). Median PFS was 19 months (95% CI, 13-28 months), and 2-year LC was 92% (95% CI, 69%-98%). Adverse event rates (highest grade per patient) were grade 1 to 2: n = 12 (31%), grade 3: n = 4 (10%), grade 4: n = 0, and grade 5: n = 3 (7.7%, all due to respiratory deterioration). Conclusions and Relevance: In this trial, use of SABR in patients with fibrotic ILD met the prespecified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT03485378.

Clinical Learning, Didactic Education, and Research Experiences of Radiation Oncology Resident Physicians in Canada.

Changes in the field of radiation oncology (RO) impacts residency training. Assessing trainee experiences is essential to inform curriculum development. We aim to explore gaps and strengths in current Canadian RO training, as we move towards competency-based medical education (CBME). An online survey was distributed to residents at all Canadian RO training programs. Surveys consisted of 66 open-ended, Likert-scale, matrix-style, and multiple-choice questions, and assessed clinical exposure, didactic teaching, professional relationships, and research experiences. Statistics were calculated from anonymized, aggregate responses. Out of 128 eligible residents, 53 responded (41% response rate). Of these, 57% were male, and 77% were Canadian medical graduates. Senior residents (PGY-4 to PGY-5) perceived insufficient exposure to lymphoma and ocular malignancies, brachytherapy for breast and esophagus malignancies, and stereotactic radiotherapy of the pancreas, prostate, and adrenal gland. Half (51%) had training on image-guided radiotherapy (IGRT) challenges, and 43% had a formal staff mentor. Most residents presented at least one research project at conferences (77%) and authored ≥ 1 publications (66%) during residency. Canadian RO residents are satisfied with their clinical training and educational experience in high-volume tumor sites and high-volume brachytherapy procedures. Areas identified for potential improvement are (1) low-volume tumor sites; (2) low-volume brachytherapy procedures; (3) low-volume stereotactic radiotherapy sites; (4) IGRT challenges; and (5) mentorship opportunities. These findings will inform future CBME curriculum revisions.

Motivations, Well-Being, and Career Aspirations of Radiation Oncology Resident Physicians in Canada.

Prior Pan-Canadian surveys of Radiation Oncology (RO) residents reveal a decrease in Canadian RO employment opportunities. Canadian RO resident levels increased from 130 in 2003, peaked at 209 in 2009, then decreased to 130 in 2017. Recognizing that RO has entered another period of transition, we re-examined resident motivations and perspectives on the job market and explored well-being and career aspirations among a contemporary cohort of Canadian RO residents. An online survey was distributed to residents at all Canadian RO training programs. Surveys consisted of 75 open-ended, Likert-scale, matrix-style, and multiple-choice questions. Student's t test compared subgroups, with statistical significance at p ≤ 0.05. Out of 128 eligible residents, 84 completed the survey (66% response rate) with representative sampling from each training year. Demographics reveal 53% male, and 85% Canadian registry-funded. Top training-related stressors were exam performance, job prospects, and physical/psychological demands of residency. Most intend to pursue fellowship post-residency (80%) and practice in Canada (88%). Few believe they can obtain staff positions treating preferred tumor sites (38%) or at preferred geographic locations (28%). Residents view job market being less competitive than 5 years ago (40%) and predict it will be less competitive in 5 years (60%). Canadian RO residents feel adequately trained, and most pursue post-residency fellowships. Current perceptions of the Canadian job market remain guarded, but appear more optimistic about the future. This update provides insights into current RO training and identifies areas that could be addressed by incoming competency-based medical education models for RO.

2b or not 2b? Shoulder function after level 2b neck dissection: A double-blind randomized controlled clinical trial.

BACKGROUND: Selective neck dissection (SND) is a mainstay of head and neck cancer treatment. A common sequela is shoulder syndrome from spinal accessory nerve (SAN) trauma. Extensive dissection in neck levels 2 and 5 leads to SAN dysfunction. However, it is not known whether limited level 2 dissection reduces SAN injury. The purpose of this double-blind randomized controlled trial was to determine whether omitting level 2b dissection would improve shoulder-related quality of life and function. METHODS: Patients with head and neck cancers undergoing surgery were randomized 1:1 to SND without level 2b dissection (group 1) or with it (group 2) on their dominant-hand side. Patients, caregivers, and assessors were blinded. The primary outcome was the change in the Neck Dissection Impairment Index (NDII) score after 6 months. An a priori calculation of the minimally important clinical difference in the NDII score was determined to establish a sample size of 15 patients per group (power = 0.8). Secondary outcomes included shoulder strength and range of motion (ROM) and SAN nerve conduction. The trial was registered at ClinicalTrials.gov (NCT00765791). RESULTS: Forty patients were enrolled, and 30 were included (15 per group). Six months after the surgery, group 2 demonstrated a significant median decrease in the NDII from the baseline (30 points) and in comparison with group 1, whose NDII dropped 17.5 points (P = .02). Shoulder ROM and SAN conduction demonstrated significant declines in group 2 (P ≤ .05). No adverse events occurred. CONCLUSIONS: Level 2b should be omitted in SND when this is oncologically safe and feasible. This allows for an optimal balance between function and cancer cure.

Meeting Minimum ESPEN Energy Recommendations Is Not Enough to Maintain Muscle Mass in Head and Neck Cancer Patients.

The relationship between dietary intake and body composition changes during cancer treatment has not been well characterized. The aim of this study was to compare dietary intake at diagnosis and end of treatment in relation to changes in muscle mass and adiposity in head and neck cancer (HNC) patients. Dietary intakes (three-day food record) and body composition using computed tomography (CT) were assessed at diagnosis (baseline) and after treatment completion (post-treatment). Skeletal muscle (SM) loss was explored as a consequence of energy and protein intake in relation to the minimum and maximum European Society of Parenteral and Enteral Nutrition (ESPEN) guidelines. Higher energy intakes (kcal/kg/day) and increases in energy intake (%) from baseline to post-treatment were correlated with attenuated muscle loss (r = 0.62, p < 0.01; r = 0.47, p = 0.04, respectively). Post-treatment protein intake demonstrated a weak positive correlation (r = 0.44, p = 0.05) with muscle loss, which did not persist when controlling for covariates. Meeting minimum ESPEN energy guidelines (25 kcal/kg/day) did not attenuate SM loss, whereas intakes >30 kcal/kg/day resulted in fewer participants losing muscle. Greater baseline adiposity correlated with greater SM loss (p < 0.001). Energy intakes of 30 kcal/kg/day may be required to protect against SM loss during treatment in HNC patients. The influence of adiposity on SM loss requires further exploration.

Is lobectomy superior to sublobar resection for early-stage small-cell lung cancer discovered intraoperatively?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: Is lobectomy superior to sublobar resection (SLR) for early-stage (cT1/2N0) small-cell lung cancer (SCLC) discovered intraoperatively? Altogether, more than 360 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Surgical treatment was shown to be superior to non-surgical treatment for early-stage SCLC in 8 papers. Seven papers showed that among patients treated surgically, lobectomy is associated with improved survival compared to SLR. One paper demonstrated both improved survival and improved freedom from local recurrence. However, 1 paper showed no difference when lobectomy was compared to anatomical segmentectomy. Three papers demonstrated significant rates of upstaging in surgical patients. Although both lobectomy and SLR are associated with improved survival compared with non-surgical treatment in early-stage SCLC, lobectomy is superior. Lobectomy was associated with improved median and overall survival, better upstaging and decreased local recurrence compared to SLR, although there is potential for selection bias and stage migration. Lobectomy should be considered the optimal approach for patients with early-stage SCLC.

Impact of Smoking on Outcomes of HPV-related Oropharyngeal Cancer Treated with Primary Radiation or Surgery.

PURPOSE: Tobacco exposure is known to affect the biological behavior of human papilloma virus (HPV)-positive oropharyngeal carcinoma (OPC) with intermediate outcomes relative to tumors that are HPV associated with no smoking exposure and smoking-related HPV-negative tumors. We aim to evaluate the impact of smoking on the outcomes of patients with HPV-associated locally advanced OPC when stratified by treatment modality. METHODS AND MATERIALS: A retrospective chart review was undertaken for 352 patients with known p16-overexpressing locally advanced OPC who were managed with curative-intent therapy from 2006 to 2015. The impact of smoking status on overall survival (OS) and recurrence-free survival were compared using the Kaplan-Meier method. RESULTS: Of the 352 patients, 67.6% (n = 238) were managed with primary chemoradiation therapy (CRT) and 32.4% (n = 114) with primary surgery ± adjuvant therapy. The median smoking pack-year was 15. Twenty-seven percent of patients were active smokers at the time of presentation, with 40.3% identifying as former smokers and 32.7% having never smoked. Median follow-up for surviving patients was 4.2 years. Current smokers had a significantly worse relapse-free survival and OS compared with never and former smokers (P = .03 and P = .0001, respectively), with outcomes significantly worsening with increasing smoking exposure. The 5-year OS for more than 10, 20, and 30 pack-year smoking history was 73.2%, 64.7%, and 59.1%, respectively. Current smokers managed with CRT had a 5-year OS of 64.2% compared with former and never smokers (93.1% and 78.2%, respectively). For current smokers managed primarily by surgery the 5-year OS was 57.6% compared with former and never smokers (69.6% and 73.5%, respectively). CONCLUSIONS: Current smokers and those with higher smoking exposure had poorer outcomes irrespective of their primary modality of treatment. Although not the specific focus of the study, definitive CRT appeared to at least be equivalent to surgery with respect to disease outcomes for patients with HPV-associated oropharyngeal cancer, regardless of smoking status.

Poor Vitamin Status is Associated with Skeletal Muscle Loss and Mucositis in Head and Neck Cancer Patients.

Mucositis and muscle wasting are two common toxicity effects of cancer treatment in head and neck cancer (HNC). There is limited data evaluating cancer treatment toxicities in relation to vitamin status. This study aimed to assess changes in vitamin status during HNC treatment in relation to body composition, inflammation and mucositis. In this prospective cohort study, dietary intakes (3-day food record), plasma levels of vitamins and C-reactive protein (CRP) were assessed at baseline (at diagnosis) and post-treatment (after 6⁻8 weeks of radiation therapy with or without chemotherapy). Computed tomography images were used to quantify body composition. Mucositis information was collected from health records of patients. Twenty-eight HNC patients (age 60 ± 10 years) completed both study time points. Patients who developed mucositis had significantly lower dietary intake of vitamins and plasma 25-hydroxy vitamin D (25-OHD) and all-trans retinol levels (p < 0.02). Patients lost a considerable amount of muscle mass (3.4 kg) and fat mass (3.6 kg) over the course of treatment. There was a trend toward greater muscle loss in patients with 25-OHD < 50 nmol/L compared to patients with 25-OHD ≥ 50 nmol/L (p = 0.07). A significant negative correlation was found between plasma all-trans retinol and CRP level at the end of treatment (p = 0.03). Poor vitamin status could be a contributing factor in developing treatment-induced toxicities.

Top 10 research priorities in head and neck cancer: Results of an Alberta priority setting partnership of patients, caregivers, family members, and clinicians.

BACKGROUND: The epidemiology, etiology, and management of head and neck cancer are evolving. Understanding the perspectives and priorities of nonresearchers regarding treatment uncertainties is important to inform future research. METHODS: Using the James Lind Alliance approach, patients, caregivers, and clinicians responded to a survey regarding their unanswered questions about treating and managing head and neck cancer. Distinct uncertainties were extracted from responses and sorted into themes. Uncertainties already answered in the literature were removed. Those remaining were ranked by patients and clinicians to develop a short list of priorities, which were discussed at a workshop and reduced to the top 10. RESULTS: One hundred sixty-one respondents posed 818 uncertainties, culminating in 77 for interim ranking and 27 for discussion at a workshop. Participants reached consensus on the top 10, which included questions on prevention, screening, treatment, and quality of life. CONCLUSION: Nonresearchers can effectively collaborate to establish priorities for future research in head and neck cancer.

A Dosimetric Comparison of Primary Chemoradiation Versus Postoperative Radiation for Locally Advanced Oropharyngeal Cancer.

Introduction Advanced-stage oropharyngeal cancer can be treated with primary chemoradiation (CRT) or primary surgery with adjuvant radiotherapy, both with similar survival outcomes. Though primary CRT prescribes a higher dose, adjuvant radiation requires irradiating the surgical bed, which may increase the high dose planned target volume (PTV). We hypothesize that the integral dose to the neck and dose to critical structures will be lower with primary CRT than adjuvant radiotherapy. Methods We selected the last 18 patients who underwent surgery and adjuvant radiotherapy at one institution between July 2015 and August 2016 with American Joint Committee on Cancer (AJCC) stage III or IVA oropharyngeal squamous cell cancer. Primary CRT treatment plans were created on the patients' preoperative computed tomography (CT) scans and prescribed 70 Gy in 33 fractions, while postoperative plans were prescribed 60 Gy in 30 fractions. The radiation doses received by organs at risk for each primary CRT plan were compared to the corresponding adjuvant radiation plan. Results  Primary CRT plans had significantly smaller high dose PTV than adjuvant radiation plans (187.3 cc (95% CI 134.9-239.7) and 466.3 cc (95% CI 356.7-575.9), p<0.0001). The neck integral dose was lower in 14 of 18 plans using primary CRT, although this was not statistically significant (p=0.5375). The primary CRT plans had lower mean doses to ipsilateral (31.8 Gy (95% CI 27.5-36.0) vs 39.3 Gy (95% CI 35.4-43.1), p=0.0009)) and contralateral parotid glands (22.5 Gy (95% CI 22.1-22.8) vs 27.6 Gy (95% CI 23.4-31.8), p=0.0238) and larynx (20.7 Gy (95% CI 19.3-22.2) vs 40.2 Gy (95% CI 30.8-46.6), p<0.0001). Conclusion Primary CRT offered a decreased neck integral dose, though it was statistically insignificant. Primary CRT plans reduce mean dose to larynx and parotid glands in comparison to postoperative radiation, which may result in lower toxicities. Clinical trials comparing primary CRT and primary surgery are warranted to compare patient toxicities.

Survival Outcomes and Patterns of Recurrence in Patients with Stage III or IV Oropharyngeal Cancer Treated with Primary Surgery or Radiotherapy.

PURPOSE: To compare and contrast the patterns of failure in patients with locally advanced squamous cell oropharyngeal cancers undergoing curative-intent treatment with primary surgery or radiotherapy +/- chemotherapy. METHODS AND MATERIALS: Two hundred and thirty-three patients with stage III or IV oropharyngeal squamous cell carcinoma who underwent curative-intent treatment from 2006-2012, were reviewed. The median length of follow-up for patients still alive at the time of analysis was 4.4 years. Data was collected retrospectively from a chart review. RESULTS: One hundred and thirty-nine patients underwent primary surgery +/- adjuvant therapy, and 94 patients underwent primary radiotherapy +/- chemotherapy (CRT). Demographics were similar between the two groups, except primary radiotherapy patients had a higher age-adjusted Charleston co-morbidity score (CCI). Twenty-nine patients from the surgery group recurred; 15 failed distantly only, seven failed locoregionally, and seven failed both distantly and locoregionally. Twelve patients recurred who underwent chemoradiotherapy; ten distantly alone, and two locoregionally. One patient who underwent radiotherapy (RT) alone failed distantly. Two and five-year recurrence-free survival rates for patients undergoing primary RT were 86.6% and 84.9% respectively. Two and five-year recurrence-free survival rates for primary surgery was 80.9% and 76.3% respectively (p=0.21). There was no significant difference in either treatment when they were stratified by p16 status or smoking status. CONCLUSIONS: Our analysis does not show any difference in outcomes for patients treated with primary surgery or radiotherapy. Although the primary pattern of failure in both groups was distant metastatic disease, some local failures may be preventable with careful delineation of target volumes, especially near the base of skull region.

Modification of the submandibular gland transfer procedure.

OBJECTIVES/HYPOTHESIS: The treatment for most advanced head and neck cancers (stage III and IV) usually includes radiation, and the most common side effect of this treatment modality is a permanent decrease in salivary production. Xerostomia is a devastating complication that significantly affects patients' quality of life by interfering with functions of taste, mastication, deglutition, and speech production. Treatment of xerostomia is varied, but one of the strategies developed by our group was to preserve one submandibular gland by surgically transferring it to the submental space and shielding it from the full dose of radiation. This procedure is proven to reduce the rate of radiation-induced xerostomia, but its main disadvantage is that it is contraindicated in oral cavity cancer. This study describes and evaluates a modification of the submandibular gland transfer (SGT) procedure, where the submandibular gland contralateral to the disease process is relocated to the parotid region. This modification has the potential of expanding the benefits of submandibular gland transfer procedures to patients with oral cavity cancers. STUDY DESIGN: Prospective feasibility study. METHODS: This study involved nine patients with a new diagnosis of advanced head and neck cancer undergoing major head and neck cancer resection with postoperative adjuvant radiation therapy. The new modified salivary gland transfer procedure was performed on all nine patients, and the glands total dose received with radiation therapy was assessed. RESULTS: All the modified SGT procedures were successful with no post-operative complications. The radiation oncology team has been able to successfully localize the transferred submandibular glands and shield them from the radiation beam postoperatively. CONCLUSIONS: We have successfully demonstrated that surgical transfer of a submandibular salivary gland to the parotid region is feasible, surgically viable, oncologically sound, and does not interfere with radiation therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2492-2496, 2016.

Present status and future directions of intraoperative radiotherapy.

In this Review, we summarise recent published work on the use of intraoperative radiotherapy to treat common tumour sites in the primary or recurrent setting. Techniques, radiobiology, and the physics of intraoperative radiotherapy are also explored. Disease sites discussed in this Review include head and neck cancer, breast cancer, sarcoma, gastrointestinal cancer, genitourinary cancer, gynaecological cancer, thoracic cancer, and palliative applications.