Oropharyngeal Cancer Staging Health Record Extraction Using Artificial Intelligence.

Importance: Accurate, timely, and cost-effective methods for staging oropharyngeal cancers are crucial for patient prognosis and treatment decisions, but staging documentation is often inaccurate or incomplete. With the emergence of artificial intelligence in medicine, data abstraction may be associated with reduced costs but increased efficiency and accuracy of cancer staging. Objective: To evaluate an algorithm using an artificial intelligence engine capable of extracting essential information from medical records of patients with oropharyngeal cancer and assigning tumor, nodal, and metastatic stages according to American Joint Committee on Cancer eighth edition guidelines. Design, Setting, and Participants: This retrospective diagnostic study was conducted among a convenience sample of 806 patients with oropharyngeal squamous cell carcinoma. Medical records of patients with staged oropharyngeal squamous cell carcinomas who presented to a single tertiary care center between January 1, 2010, and August 1, 2020, were reviewed. A ground truth cancer stage dataset and comprehensive staging rule book consisting of 135 rules encompassing p16 status, tumor, and nodal and metastatic stage were developed. Subsequently, 4 distinct models were trained: model T (entity relationship extraction) for anatomical location and invasion state, model S (numerical extraction) for lesion size, model M (sequential classification) for metastasis detection, and a p16 model for p16 status. For validation, results were compared against ground truth established by expert reviewers, and accuracy was reported. Data were analyzed from March to November 2023. Main Outcomes and Measures: The accuracy of algorithm cancer stages was compared with ground truth. Results: Among 806 patients with oropharyngeal cancer (mean [SD] age, 63.6 [10.6] years; 651 males [80.8%]), 421 patients (52.2%) were positive for human papillomavirus. The artificial intelligence engine achieved accuracies of 55.9% (95% CI, 52.5%-59.3%) for tumor, 56.0% (95% CI, 52.5%-59.4%) for nodal, and 87.6% (95% CI, 85.1%-89.7%) for metastatic stages and 92.1% (95% CI, 88.5%-94.6%) for p16 status. Differentiation between localized (stages 1-2) and advanced (stages 3-4) cancers achieved 80.7% (95% CI, 77.8%-83.2%) accuracy. Conclusion and Relevance: This study found that tumor and nodal staging accuracies were fair to good and excellent for metastatic stage and p16 status, with clinical relevance in assigning optimal treatment and reducing toxic effect exposures. Further model refinement and external validation with electronic health records at different institutions are necessary to improve algorithm accuracy and clinical applicability.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial.

BACKGROUND: Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer. METHODS AND FINDINGS: This prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial. CONCLUSIONS: MRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials. TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT04431674.

Stereotactic body radiotherapy for distant metastases to the head and neck.

PURPOSE: To report clinical outcomes for patients with metastatic disease to the head and neck (HN) treated with stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of patients treated with SBRT to HN sites from 2012 to 2020 was conducted. Treatment indications included the following: oligometastases, oligoprogression, and control a dominant area of progression (DAP). Kaplan-Meier method was used to estimate local control (LC), regional control (RC), overall survival (OS), and progression-free survival (PFS). Univariable (UVA) and multivariable analyses (MVA) were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: Fifty-six patients (58 lesions) were analysed with a median follow-up of 16 months. Primary sites included lung (25.0%), kidney (19.6%), breast (19.6%) and other (35.8%). SBRT indications were as follows: oligometastases (42.9%), oligoprogression (19.6%) and local control of a dominant area of progression (37.5%). Most patients received SBRT to a single neck node (n = 47, 81.0%). Median SBRT dose was 40 Gy (range 25-50 Gy) in five fractions, with a median biologically effective dose (BED10) of 72 Gy (range 37.5-100 Gy). One- and 2-year LC and RC rates were 97.6% and 72.7% as well as 100% and 86.7%, respectively. Median OS was 19.2 months (95% [CI] 14.8-69.4), and median PFS was 7.4 months (95% [CI] 5.2-11.9). The 1-year OS and PFS rates for oligometastases, oligoprogression and DAP were 95.8%, 63.6% and 38.1% (p = 0.0039) as well as 56.5%, 27.3% and 19.1% (p = 0.0004), respectively. On MVA, treatment indication and histology were predictive for OS, while indication and prior systemic therapy were predictive for PFS. Cumulative late grade 3 + toxicity rate was 11.3%, without grade 5 events. CONCLUSION: The use of SBRT for metastatic disease to the HN provided excellent LC rates with low rates of regional failure and an acceptable toxicity profile, highlighting its utility in these patients. Patients with oligometastatic disease had better OS and PFS than others.

Stereotactic Body Radiotherapy for Extracranial Oligometastatic Disease from Head and Neck Primary Cancers: A Systematic Review and Meta-Analysis.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. METHODS: A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint. RESULTS: Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. CONCLUSIONS: SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.

Quantitative US Delta Radiomics to Predict Radiation Response in Individuals with Head and Neck Squamous Cell Carcinoma.

Purpose To investigate the role of quantitative US (QUS) radiomics data obtained after the 1st week of radiation therapy (RT) in predicting treatment response in individuals with head and neck squamous cell carcinoma (HNSCC). Materials and Methods This prospective study included 55 participants (21 with complete response [median age, 65 years {IQR: 47-80 years}, 20 male, one female; and 34 with incomplete response [median age, 59 years {IQR: 39-79 years}, 33 male, one female) with bulky node-positive HNSCC treated with curative-intent RT from January 2015 to October 2019. All participants received 70 Gy of radiation in 33-35 fractions over 6-7 weeks. US radiofrequency data from metastatic lymph nodes were acquired prior to and after 1 week of RT. QUS analysis resulted in five spectral maps from which mean values were extracted. We applied a gray-level co-occurrence matrix technique for textural analysis, leading to 20 QUS texture and 80 texture-derivative parameters. The response 3 months after RT was used as the end point. Model building and evaluation utilized nested leave-one-out cross-validation. Results Five delta (Δ) parameters had statistically significant differences (P < .05). The support vector machines classifier achieved a sensitivity of 71% (15 of 21), a specificity of 76% (26 of 34), a balanced accuracy of 74%, and an area under the receiver operating characteristic curve of 0.77 on the test set. For all the classifiers, the performance improved after the 1st week of treatment. Conclusion A QUS Δ-radiomics model using data obtained after the 1st week of RT from individuals with HNSCC predicted response 3 months after treatment completion with reasonable accuracy. Keywords: Computer-Aided Diagnosis (CAD), Ultrasound, Radiation Therapy/Oncology, Head/Neck, Radiomics, Quantitative US, Radiotherapy, Head and Neck Squamous Cell Carcinoma, Machine Learning Clinicaltrials.gov registration no. NCT03908684 Supplemental material is available for this article. © RSNA, 2024.

Lymph node yield: Impact on oncologic outcomes in oral cavity cancer.

BACKGROUND: Lymph node metastases are associated with poor prognosis in oral cavity squamous cell carcinoma (OCSCC). In other cancers, clinical guidelines on the number of lymph nodes removed during primary surgery, lymph node yield (LNY), exist. Here, we evaluated the prognostic capacity of LNY on regional failure, locoregional recurrence, and disease-free survival (DFS) in patients with OCSCC treated by primary neck surgery. METHODS: This retrospective cohort study took place at Sunnybrook Health Sciences Centre in Toronto, Canada and involved a chart review of all adult patients with treatment-naive OCSCC undergoing primary neck dissection. For each outcome, we first used the maximally selected rank statistics and an optimism-corrected concordance to identify an optimal threshold of LNY. We then used a multivariable Cox proportional hazards model to assess the association between high LNY (>threshold) and each outcome. RESULTS: Among the 579 patients with OCSCC receiving primary neck dissection, 61.7% (n = 357) were male with a mean age of 62.9 years (standard deviation: 13.1) at cancer diagnosis. When adjusting for sociodemographic and clinical factors, LNY >15 was significantly associated with improved DFS (adjusted HR [aHR]: 0.73, 95% CI: 0.54-0.98), locoregional recurrence (aHR: 0.68, 95% CI: 0.49-0.95), and regional failure (aHR: 0.61, 95% CI: 0.39-0.93). CONCLUSIONS: Our study findings suggested high LNY to be a strong independent predictor of various patient-level quality of surgical care metrics. The optimal LNY we found (15) was lower than the conventionally recommended (18), which calls for further research to establish validity in practice.

Patient-reported experience with the use of Mepitel Film for prevention of acute radiation dermatitis in breast cancer.

BACKGROUND AND PURPOSE: Mepitel Film (MF) has been demonstrated to reduce the severity of radiation dermatitis (RD) in patients receiving breast cancer radiotherapy (RT). The objective of this study was to characterize patient-reported experience with MF use, including its impact on daily activities and wellbeing. MATERIALS AND METHODS: This single-institution study analyzed anonymized responses to a questionnaire completed by patients who used MF for the prevention of RD during breast cancer RT. RESULTS: Of the 254 patients contacted, 192 patients completed the survey. Most patients disagreed or strongly disagreed that MF limited their ability to perform their daily activities, including household chores (88%, n = 169/191), their ability to work (83%, n = 157/189), or their ability to sleep (85%, n = 163/191). Furthermore, patients agreed or strongly agreed MF was comfortable on their skin (67%, n = 126/189) and protected their skin from rubbing against clothing (86%, n = 161/188). Some patients agreed or strongly agreed that MF affected their ability to shower (31%, n = 50/162), wear bras (28%, n = 51/185), and impacted their level of pruritus (35%, n = 67/189). However, most patients agreed or strongly agreed that their overall experience with MF was positive (92%, n = 173/189) and would recommend MF to a friend undergoing breast cancer RT (88%, n = 166/188). CONCLUSION: MF use is associated with positive patient-reported experience during breast RT with minimal impact on daily activities.

COVID-19 pandemic impact on the potential exacerbation of screening mammography disparities: A population-based study in Ontario, Canada.

Strategies to ramp up breast cancer screening after COVID-19 require data on the influence of the pandemic on groups of women with historically low screening uptake. Using data from Ontario, Canada, our objectives were to 1) quantify the overall pandemic impact on weekly bilateral screening mammography rates (per 100,000) of average-risk women aged 50-74 and 2) examine if COVID-19 has shifted any mammography inequalities according to age, immigration status, rurality, and access to material resources. Using a segmented negative binomial regression model, we estimated the mean change in rate at the start of the pandemic (the week of March 15, 2020) and changes in weekly trend of rates during the pandemic period (March 15-December 26, 2020) compared to the pre-pandemic period (January 3, 2016-March 14, 2020) for all women and for each subgroup. A 3-way interaction term (COVID-19*week*subgroup variable) was added to the model to detect any pandemic impact on screening disparities. Of the 3,481,283 mammograms, 8.6 % (n = 300,064) occurred during the pandemic period. Overall, the mean weekly rate dropped by 93.4 % (95 % CI 91.7 % - 94.8 %) at the beginning of COVID-19, followed by a weekly increase of 8.4 % (95 % CI 7.4 % - 9.4 %) until December 26, 2020. The pandemic did not shift any disparities (all interactions p > 0.05) and that women who were under 60 or over 70, immigrants, or with a limited access to material resources had persistently low screening rate in both periods. Interventions should proactively target these underserved populations with the goals of reducing advanced-stage breast cancer presentations and mortality.

Interventions for Concerning Patient-Reported Outcomes in Routine Cancer Care: A Systematic Review.

IMPORTANCE: Collecting patient-reported outcomes (PROs) in routine cancer care improves patient-clinician communication, decision making, and overall patient satisfaction. Recommendations exist regarding standardized ways to collect, store, and interpret PRO data. However, evidence on incorporating PROs into cancer process of care, especially the type of HIs that are warranted after observing a concerning PRO and the effectiveness of these HIs are lacking. OBJECTIVE: This study summarizes HIs triggered after PRO completion and their effectiveness in improving patient outcomes for adults being treated for cancer types that are resource intensive and associated with high symptom burden [i.e., gastrointestinal (GI), lung, and head and neck cancer (HNC)]. Secondary outcomes included factors associated with poor implementation of PROs. EVIDENCE REVIEW: A literature search of peer-reviewed publications on MEDLINE, CINAHL Plus, APA PsycInfo, Scopus, and Cochrane was conducted following PRISMA guidelines from 1 January 2012, to 31 July 2022. Trial and real-world studies describing HIs after PRO completion for adult patients being treated for GI, lung, and HNC were included. Sixteen studies involving 144,496 patients were included. The Joanna Briggs Institute critical appraisal checklist was used to assess risk of bias. FINDINGS: Of the 16 included studies, 5 included patients with HNC. Commonly used PRO measurement tools were the PRO-CTCAE and ESAS. Only three studies reported specific HIs delivered in response to concerning PROs and measured their effectiveness on patient outcomes. In all three studies, these HIs significantly improved cancer-related care. The most common HIs undertaken in response to concerning PROs were referrals to other specialists/allied healthcare professionals, medication changes, or self-management advice. Provider-related barriers to PRO measurement and delivery included the overwhelming number of alerts, the time required to address each PRO and the unclear role of healthcare providers in response to these alerts. Patient-related barriers included lower digital literacy and socioeconomic status, older age, rural living, and patients suffering from GI and HNC. CONCLUSIONS AND RELEVANCE: This review highlights that PRO-triggered HIs are heterogenous and can improve patient quality of life. Further studies are necessary to determine the types of interventions with the greatest impact on patient care and outcomes.

Tumor volumes in T3 supraglottic cancers treated with radiotherapy in the modern era: A study of the Canadian Head & Neck Collaborative Research Initiative.

PURPOSE: To evaluate the association of primary tumor volume (TV) with overall survival (OS) and disease-free survival (DFS) in T3 N0-3M0 supraglottic cancers treated with intensity-modulated radiotherapy (IMRT). METHODS: This was a retrospective cohort study involving 239 patients diagnosed with T3 N0-3M0 supraglottic cancers between 2002 and 2018 from seven regional cancer centers in Canada. Clinical data were obtained from the patient records. Supraglottic TV was measured by neuroradiologists on diagnostic imaging. Kaplan-Meier method was used for survival probabilities, and a restricted cubic spline Cox proportional hazards regression analysis was used to analyze TV associations with OS and DFS. RESULTS: Mean (SD) of participants was 65.2 (9.4) years; 176 (73.6%) participants were male. 90 (38%) were N0, and 151 (64%) received concurrent systemic therapy. Mean TV (SD) was 11.37 (12.11) cm3 . With mean follow up (SD) of 3.28 (2.60) years, 2-year OS was 72.7% (95% CI 66.9%-78.9%) and DFS was 53.6% (47.4%-60.6%). Increasing TV was associated (per cm3 increase) with worse OS (HR, 1.01, 95% CI 1.00-1.02, p < 0.01) and DFS (HR, 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSIONS: Increasing primary tumor volume is associated with worse OS and DFS in T3 supraglottic cancers treated with IMRT, with no clear threshold. The findings suggest that patients with larger tumors and poor baseline laryngeal function may benefit from upfront laryngectomy with adjuvant radiotherapy.

Locoregional Ablative Radiation Therapy for Patients With Breast Cancer Unsuitable for Surgical Resection.

PURPOSE: Patients with breast cancer who are unsuitable for surgical resection are typically managed with palliative systemic therapy alone. We report outcomes of 5-fraction ablative radiation therapy for nonresected breast cancers. METHODS AND MATERIALS: This is a retrospective analysis of an institutional registry of patients with breast cancer who were unsuitable for resection and underwent 35 to 40 Gy/5 fractions to the primary breast tumor or regional lymph nodes from 2014 to 2021. Primary outcomes were cumulative incidence of local failure and grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). RESULTS: We reviewed 57 patients who received 61 treatment courses (median age of 81 years; range, 38-99). Unresectable tumor (10%), patient refusal (18%), medical inoperability (35%), and metastatic disease (37%) were the causes of not having surgery. Five patients (8%) had previously undergone adjuvant locoregional radiation therapy. Fifty-four percent (n = 33/61) of treatment courses targeted the breast only, 31% (n = 19/61) both the breast and lymph nodes, and 15% (n = 9/61) the lymph nodes only. Sixty-seven percent (n = 35/52) of the courses that targeted the breast were delivered with partial breast irradiation and 33% (n = 17/52) with whole breast radiation therapy (median dose of 25 Gy in 5 fractions) ± simultaneous integrated boost to the primary tumor. Most primary tumors (65%, n = 34/52) and target lymph nodes (61%, n = 17/28) were treated with a dose of 35 Gy in 5 fractions. Most treatments (52%) were delivered with intensity modulated radiation therapy (IMRT). Radiation therapy was delivered daily (20%), every other day (18%), twice weekly (36%), or weekly (26%). The 2-year cumulative incidence of local failure was 11.4% and grade≥3 toxicity was 15.1%. The grade ≥3 toxicity was 6.5% for IMRT treatments, versus 7.7% for non-IMRT treatments targeting partial breast or lymph nodes (hazard ratio, 1.13, P = .92), versus 38.9% for non-IMRT treatments targeting the entire breast (hazard ratio, 6.91, P = .023). All grade ≥3 toxicity cases were radiation dermatitis. No cases of brachial plexopathy were observed. CONCLUSIONS: Thirty-five to 40 Gy in 5 fractions is a safe and effective breast stereotactic body radiation therapy (SBRT) regimen and may be an attractive option for patients who are not surgical candidates. Highly conformal techniques (ie, IMRT or partial breast irradiation) were associated with a reduced risk of toxicity and should be the preferred treatment approaches.

Perceptions of healthcare professionals on the use of Mepitel Film for the prevention of acute radiation dermatitis in breast cancer.

INTRODUCTION: Randomized clinical trials support Mepitel Film (MF) as a prophylactic treatment for radiation dermatitis (RD) in patients undergoing breast radiotherapy. Although several studies have canvassed the opinion of patients on using MF, no such studies have been done to investigate the perception of healthcare professionals (HCPs). The objective of this study was therefore to investigate the perceptions of HCPs on MF as a treatment option for RD. METHODS: Anonymized responses to a web-based survey sent to HCPs at a single institution managing patients using MF during breast radiotherapy were analyzed. RESULTS: Of the 28 HCPs contacted, 22 completed the survey, including 6 radiation oncologists (ROs), 11 radiation therapists (RTTs), and 5 nurses. Most HCPs reported MF was better at preventing severe RD than the standard of care and improved radiation-induced skin reactions (n = 20/22, 91%, and n = 19/22, 86%, respectively). MF was recommended for mastectomy patients without reconstruction (n = 15/21, 71%). The majority of HCPs believed that patients' families could be trained to apply and remove MF (n = 19/22, 86%). Many HCPs perceived that implementation of MF would be difficult in terms of maintaining patient flow and wide-scale implementation within their institution (n = 11/22, 50%, and n = 10/22, 46%, respectively). Most HCPs perceived that fewer than 50% of their patients could afford MF if priced at $100 CAD (n = 15/20, 75%). CONCLUSION: These findings provide insights into the possibility of MF to be incorporated into standard practice of care for RD. Although most HCPs were satisfied with MF as a prophylactic treatment for RD, there are concerns about its resource-intensive operationalization and financial accessibility to patients. Future research should focus on ways to improve HCP experience with MF and to improve its implementation into clinical settings as standard of care.

The Evolving Role of Stereotactic Body Radiation Therapy for Head and Neck Cancer: Where Do We Stand?

Stereotactic body radiation therapy (SBRT) is a precise and conformal radiation therapy (RT) that aims to deliver a high dose of radiation to the tumor whilst sparing surrounding normal tissue, making it an attractive option for head and neck cancer (HNC) patients who are not suitable for the traditional long course of RT with comprehensive RT target volume. Definitive SBRT for HNC has been investigated in different settings, including early stage glottis cancer, and as an alternative to brachytherapy boost after external beam RT. It is also used as a primary treatment option for elderly or medically unfit patients. More recently, an SBRT combination with immunotherapy in the neoadjuvant setting for HNC showed promising results. Salvage or adjuvant SBRT for HNC can be used in appropriately selected cases. Future studies are warranted to determine the optimum dose and fractionation schedules in any of these indications.

Novel MRI-guided focussed ultrasound stimulated microbubble radiation enhancement treatment for breast cancer.

Preclinical studies have demonstrated focused ultrasound (FUS) stimulated microbubble (MB) rupture leads to the activation of acid sphingomyelinase-ceramide pathway in the endothelial cells. When radiotherapy (RT) is delivered concurrently with FUS-MB, apoptotic pathway leads to increased cell death resulting in potent radiosensitization. Here we report the first human trial of using magnetic resonance imaging (MRI) guided FUS-MB treatment in the treatment of breast malignancies. In the phase 1 prospective interventional study, patients with breast cancer were treated with fractionated RT (5 or 10 fractions) to the disease involving breast or chest wall. FUS-MB treatment was delivered before 1st and 5th fractions of RT (within 1 h). Eight patients with 9 tumours were treated. All 7 evaluable patients with at least 3 months follow-up treated for 8 tumours had a complete response in the treated site. The maximum acute toxicity observed was grade 2 dermatitis in 1 site, and grade 1 in 8 treated sites, at one month post RT, which recovered at 3 months. No RT-related late effect or FUS-MB related toxicity was noted. This study demonstrated safety of combined FUS-MB and RT treatment. Promising response rates suggest potential strong radiosensitization effects of the investigational modality.Trial registration: clinicaltrials.gov, identifier NCT04431674.

Mepitel film for the prevention and treatment of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the efficacy of Mepitel film in preventing or treating acute radiation dermatitis (RD) in patients with breast cancer in randomized controlled trials (RCTs). METHODS: Embase, APA PsychInfo, Journals@Ovid Full Text, Ovid MEDLINE, PubMed, and Cochrane Trials were searched until December 12, 2022, to identify RCTs on the use of Mepitel film for preventing or treating acute RD from breast cancer radiotherapy. Per-protocol analysis was used to compare outcomes, calculate pooled effect sizes, odds ratio (OR), and 95% confidence intervals (CI), and to create forest plots using random effects analysis in RevMan 5.4. RESULTS: Three RCTs were included in this review. Mepitel film significantly reduced the incidence of grade 3 RD (OR 0.15 95% CI 0.06, 0.37, p<0.0001) and grade 2 or 3 RD (OR 0.16 95% CI 0.04, 0.65, p=0.01) as scored on either the CTCAE or the RTOG scale. Additionally, Mepitel film significantly reduced RISRAS mean scores assessed by patients and combined researcher and patient (standardized mean difference (SMD) -7.59, 95% CI -14.42, -0.76, p=0.03; SMD -15.36, 95% CI -30.01, -0.71 p=0.04) but not the researcher component of the assessment tool (SMD -17.55, 95% CI -36.94, 1.84, p=0.08). CONCLUSION: Mepitel film reduced the incidence of acute RD and improved patient-reported outcomes with minimal side effects, the main one being itchiness. Future research should assess the feasibility of Mepitel film with respect to specific patient-reported outcomes such as health-related quality of life issues associated with its use.

The protective role of postoperative radiation therapy in low and intermediate grade major salivary gland malignancies: A study of the Canadian Head and Neck Collaborative Research Initiative.

BACKGROUND: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands. METHODS: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution. RESULTS: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins. CONCLUSIONS: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins.

Cine MRI-based analysis of intrafractional motion in radiation treatment planning of head and neck cancer patients.

PURPOSE/OBJECTIVE(S): To investigate intrafraction motion of (HN) target volumes and to determine patient-specific planning target volume (PTV) margins. MATERIALS/METHODS: MR-cine imaging was performed for radiation treatment planning in HN cancer patients treated with definitive EBRT (n = 62) or SBRT (n = 4) on a 1.5 T MRI between 2017-2019. Dynamic MRI scans (sagittal orientation, 2 × 82 × 7 mm3 resolution), ranging from 3-5 min and 900-1500 images, were acquired. The position of the maximum tumor displacement along each direction in the anterior/posterior (A/P) and superior/inferior (S/I) position was recorded and analyzed to determine average PTV margins. RESULTS: Primary tumor sites (n = 66) were oropharynx (n = 39), larynx (n = 24) and hypopharynx (n = 3). PTV margins for A/P/S/I positions were 4.1/4.4/5.0/6.2 mm and 4.9/4.3/6.7/7.7 mm for oropharyngeal and laryngeal/hypopharyngeal cancers when accounting for all motion. V100 for PTV was calculated and compared to the original plans. The mean drop in PTV coverage was in most cases under 5%. For a subset of patients with 3 mm plans available, V100 for PTV had more substantial decreases in coverage averaging 8.2% - and 14.3% for oropharyngeal and laryngeal/hypopharynx plans, respectively. CONCLUSION: The use of MR-cine in treatment planning allows for quantification of tumor motion during swallow and resting periods and should be accounted for during treatment planning. With motion considered, the derived margins may exceed the commonly used 3-5 mm PTV margins. Quantification and analysis of tumor and patient-specific PTV margins is a step towards real-time MRI guidance adaptive radiotherapy.

A comparison of acute patient-reported outcomes in breast cancer patients with and without regional nodal irradiation using the ESAS and PRFS tool.

BACKGROUND AND PURPOSE: Regional nodal irradiation (RNI) is commonly administered in patients with breast cancer with node-positive disease to prevent cancer recurrence. The purpose of this study is to identify whether RNI is associated with greater acute symptom burden from baseline to 1 to 3 months post completion of radiotherapy (RT) when compared to localized RT. MATERIALS AND METHODS: Patient and treatment characteristics were collected prospectively for breast cancer patients with and without RNI from February 2018 to September 2020. The Edmonton Symptom Assessment System (ESAS) and Patient-Reported Functional Status (PRFS) tool were completed by patients at baseline, weekly during RT, and at a 1- to 3-month follow-up visit. The Wilcoxon rank-sum or Fisher exact tests were used to compare variables between patients with or without RNI. RESULTS: A total of 781 patients were included in the analysis. Baseline symptom reporting was similar between cohorts, with the exception of PRFS scores (p = 0.0023), which were worse in patients receiving RNI. Across all time points, differences in outcomes between cohorts were minimal, except for lack of appetite (p = 0.03) and PRFS scores (p = 0.049), which were significantly aggravated in patients treated with RNI. CONCLUSION: There is insufficient evidence to suggest that RNI is associated with greater symptom burden as assessed with the ESAS. Further research should be conducted over a longer time period to determine the impact of late effects of RNI on patient-reported symptoms.

Comparison of neoadjuvant versus adjuvant chemotherapy for breast cancer patients prior to receiving radiation therapy using Edmonton Symptom assessment system (ESAS) scores.

BACKGROUND AND PURPOSE: Patients undergoing radiotherapy (RT) for breast cancer may receive adjuvant or neoadjuvant chemotherapy prior to the initiation of RT treatment. In the present study, baseline Edmonton Symptom Assessment System (ESAS) scores of patients who received neoadjuvant and adjuvant chemotherapy were collected prior to RT and compared to assess the association of each chemotherapy intent with pre-RT symptom burden. MATERIAL AND METHODS: The ESAS and Patient-Reported Functional Status (PRFS) tools were used to collect patient-reported symptoms at baseline. Patient and treatment-related factors were collected prospectively from February 2018 to September 2020. Univariate general linear regression analysis was applied to compare baseline scores between adjuvant and neoadjuvant chemotherapy patients. RESULTS: A total of 338 patients were included for analysis. Comparison of baseline ESAS scores revealed that patients who received adjuvant chemotherapy were more likely to report higher scores, reflecting higher symptom burden, compared to patients receiving neoadjuvant chemotherapy, including tiredness (p = 0.005), lack of appetite (p = 0.0005), shortness of breath (p < 0.0001), and PRFS (p = 0.012). CONCLUSION: This study suggests an association between patients who have received adjuvant chemotherapy for breast cancer and higher RT baseline ESAS scores when compared to patients who received neoadjuvant chemotherapy. Due to these findings, considerations should be made by healthcare providers of the symptom burden during RT for patients who receive adjuvant chemotherapy.