Assessment of shoulder position variation and its impact on IMRT and VMAT doses for head and neck cancer

<p>Abstract</p> <p>Background</p> <p>For radiotherapy of the head and neck, 5-point mask immobilization is used to stabilize the shoulders. Still, the daily position of the shoulders during treatment may be different from the position in the treatment plan despite correct isocenter setup. The purpose of this study was to determine the interfractional displacement of the shoulders relative to isocenter over the course of treatment and the associated dosimetric effect of this displacement.</p> <p>Methods</p> <p>The extent of shoulder displacements relative to isocenter was assessed for 10 patients in 5-point thermoplastic masks using image registration and daily CT-on-rails scans. Dosimetric effects on IMRT and VMAT plans were evaluated in Pinnacle based on simulation CTs modified to represent shoulder shifts between 3 and 15 mm in the superior-inferior, anterior-posterior, and right-left directions. The impact of clinically observed shoulder shifts on the low-neck dose distributions was examined.</p> <p>Results</p> <p>Shoulder motion was 2-5 mm in each direction on average but reached 20 mm. Superior shifts resulted in coverage loss, whereas inferior shifts increased the dose to the brachial plexus. These findings were generally consistent for both IMRT and VMAT plans. Over a course of observed shifts, the dose to 99% of the CTV decreased by up to 101 cGy, and the brachial plexus dose increased by up to 72 cGy.</p> <p>Conclusions</p> <p>he position of the shoulder affects target coverage and critical structure dose, and may therefore be a concern during the setup of head and neck patients, particularly those with low neck primary disease.</p

Using the Persuasive Design Model to Refine a Novel Stimuli Responsive Polymeric Sensor in Head and Neck Cancer Patients

https://openworks.mdanderson.org/sumexp22/1143/thumbnail.jp

Factors Associated with Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported RTOG trials of concurrent chemoradiotherapy for locally advanced SCCHN (RTOG 91-11; 97-03; and 99-14). Severe late toxicity was defined in this secondary analysis as chronic Grade 3-4 pharyngeal/laryngeal toxicity (RTOG/EORTC late toxicity scoring system) and/or requirement for a feeding tube ≥2 years after registration and/or potential treatment-related death (e.g. pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pre-treatment and treatment potential factors. Results A total of 230 patients were evaluable for this analysis, 99 cases (patients with severe late toxicities) and 131 controls; thus 43% of evaluable patients had a severe late toxicity. On multivariable analysis, significant variables correlated with the development of severe late toxicity were older age (odds ratio 1.05 per year; p = 0.001); advanced T-stage (odds ratio 3.07; p=0.0036); larynx/hypopharynx primary site (odds ratio 4.17; p=0.0041); and neck dissection after chemo-RT (odds ratio 2.39; p=0.018). Conclusions Severe late toxicity following CCRT is common. Older age, advanced T-stage, and larynx/ hypopharynx primary site were strong independent risk American Society of Clinical Oncology. Machtay, M. et al: J. Clin. Oncol. 26 (21), 2008:3582-3589

Risk and Clinical Risk Factors associated With Late Lower Cranial Neuropathy in Long-Term oropharyngeal Squamous Cell Carcinoma Survivors

IMPORTANCE: Lower cranial neuropathy (LCNP) is a rare, but permanent, late effect of radiotherapy and other cancer therapies. Lower cranial neuropathy is associated with excess cancer-related symptoms and worse swallowing-related quality of life. Few studies have investigated risk and clinical factors associated with late LCNP among patients with long-term survival of oropharyngeal squamous cell carcinoma (OPSCC survivors). OBJECTIVE: to estimate the cumulative incidence of and identify clinical factors associated with late LCNP among long-term OPSCC survivors. DESIGN, SETTING, AND PARTICIPANTS: This single-institution cohort study included disease-free adult OPSCC survivors who completed curative treatment from January 1, 2000, to December 31, 2013. Exclusion criteria consisted of baseline LCNP, recurrent head and neck cancer, treatment at other institutions, death, and a second primary, persistent, or recurrent malignant neoplasm of the head and neck less than 3 months after treatment. Median survival of OPSCC among the 2021 eligible patients was 6.8 (range, 0.3-18.4) years. Data were analyzed from October 12, 2019, to November 13, 2020. MAIN OUTCOMES AND MEASURES: Late LCNP events were defined by neuropathy of the glossopharyngeal, vagus, and/or hypoglossal cranial nerves at least 3 months after cancer therapy. Cumulative incidence of LCNP was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were fit. RESULTS: Among the 2021 OPSCC survivors included in the analysis of this cohort study (1740 [86.1%] male; median age, 56 [range, 28-86] years), 88 (4.4%) were diagnosed with late LCNP, with median time to LCNP of 5.4 (range, 0.3-14.1) years after treatment. Cumulative incidence of LCNP was 0.024 (95% CI, 0.017-0.032) at 5 years, 0.061 (95% CI, 0.048-0.078) at 10 years, and 0.098 (95% CI, 0.075-0.128) at 15 years of follow-up. Multivariable Cox proportional hazards regression identified T4 vs T1 classification (hazard ratio [HR], 3.82; 95% CI, 1.85-7.86) and accelerated vs standard radiotherapy fractionation (HR, 2.15; 95% CI, 1.34-3.45) as independently associated with late LCNP status, after adjustment. Among the subgroup of 1986 patients with nonsurgical treatment, induction chemotherapy regimens including combined docetaxel, cisplatin, and fluorouracil (TPF) (HR, 2.51; 95% CI, 1.35-4.67) and TPF with cetuximab (HR, 5.80; 95% CI, 1.74-19.35) along with T classification and accelerated radiotherapy fractionation were associated with late LCNP status after adjustment. CONCLUSIONS AND RELEVANCE: This single-institution cohort study found that, although rare in the population overall, cumulative risk of late LCNP progressed to 10% during the survivors\u27 lifetime. As expected, clinical factors associated with LCNP primarily reflected greater tumor burden and treatment intensity. Further efforts are necessary to investigate risk-reduction strategies as well as surveillance and management strategies for this disabling late effect of cancer treatment

The impact of induction and/or concurrent chemoradiotherapy on acute and late patient-reported symptoms in oropharyngeal cancer:Application of a mixed-model analysis of a prospective observational cohort registry

BACKGROUND The goal of this study was to comprehensively investigate the association of chemotherapy with trajectories of acute symptom development and late symptom recovery in patients with oropharyngeal cancer (OPC) by comparing symptom burden between induction chemotherapy followed by concurrent chemoradiotherapy (ICRT), concurrent chemo-radiotherapy (CRT), or radiotherapy (RT) alone.METHODS Among a registry of 717 patients with OPC, the 28-item patient-reported MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) symptoms were collected prospectively at baseline, weekly during RT, and 1.5, 3 to 6, 12, and 18 to 24 months after RT. The effect of the treatment regimen (ICRT, CRT, and RT alone) was examined with mixed-model analyses for the acute and late period. In the CRT cohort, the chemotherapy agent relationship with symptoms was investigated.RESULTS Chemoradiation (ICRT/CRT) compared with RT alone resulted in significantly higher acute symptom scores in the majority of MDASI-HN symptoms (ie, 21 out of 28). No late symptom differences between treatment with or without chemotherapy were observed that were not attributable to ICRT. Nausea was lower for CRT with carboplatin than for CRT with cisplatin; cetuximab was associated with particularly higher scores for acute and late skin, mucositis, and 6 other symptoms. The addition of ICRT compared with CRT or RT alone was associated with a significant increase in numbness and shortness of breath.CONCLUSION The addition of chemotherapy to definitive RT for OPC patients was associated with significantly worse acute symptom outcomes compared with RT alone, which seems to attenuate in the late posttreatment period. Moreover, induction chemotherapy was specifically associated with worse numbness and shortness of breath during and after treatment.LAY SUMMARYChemotherapy is frequently used in addition to radiotherapy cancer treatment, yet the (added) effect on treatment-induced over time is not comprehensively investigatedThis study shows that chemotherapy adds to the symptom severity reported by patients, especially during treatment</p

Head and neck cancer predictive risk estimator to determine control and therapeutic outcomes of radiotherapy (HNC-PREDICTOR):development, international multi-institutional validation, and web implementation of clinic-ready model-based risk stratification for head and neck cancer

Background: Personalised radiotherapy can improve treatment outcomes of patients with head and neck cancer (HNC), where currently a ‘one-dose-fits-all’ approach is the standard. The aim was to establish individualised outcome prediction based on multi-institutional international ‘big-data’ to facilitate risk-based stratification of patients with HNC. Methods: The data of 4611 HNC radiotherapy patients from three academic cancer centres were split into four cohorts: a training (n = 2241), independent test (n = 786), and external validation cohorts 1 (n = 1087) and 2 (n = 497). Tumour- and patient-related clinical variables were considered in a machine learning pipeline to predict overall survival (primary end-point) and local and regional tumour control (secondary end-points); serially, imaging features were considered for optional model improvement. Finally, patients were stratified into high-, intermediate-, and low-risk groups. Results: Performance score, AJCC8th stage, pack-years, and Age were identified as predictors for overall survival, demonstrating good performance in both the training cohort (c-index = 0.72 [95% CI, 0.66–0.77]) and in all three validation cohorts (c-indices: 0.76 [0.69–0.83], 0.73 [0.68–0.77], and 0.75 [0.68–0.80]). Excellent stratification of patients with HNC into high, intermediate, and low mortality risk was achieved; with 5-year overall survival rates of 17–46% for the high-risk group compared to 92–98% for the low-risk group. The addition of morphological image feature further improved the performance (c-index = 0.73 [0.64–0.81]). These models are integrated in a clinic-ready interactive web interface: https://uic-evl.github.io/hnc-predictor/ Conclusions: Robust model-based prediction was able to stratify patients with HNC in distinct high, intermediate, and low mortality risk groups. This can effectively be capitalised for personalised radiotherapy, e.g., for tumour radiation dose escalation/de-escalation

Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients [PIRATES]:A Phase I safety and feasibility trial of MRI-guided adaptive particle radiotherapy

Introduction: Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With “Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients” (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach. Methods: The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk of dose-limiting toxicities (DLTs): 1) sparing surrounding normal tissue from extraneous dose with intensity-modulated proton therapy, 2) mid-treatment hybrid hyper-fractionation for radiobiologic normal tissue sparing; 3) Magnetic Resonance Imaging (MRI) guided mid-treatment boost volume adaptation, and 4) iso-effective restricted organ-at-risk dosing to mucosa and bone tissues. The time-to-event Bayesian optimal interval (TITE-BOIN) design is employed to address the challenge of the long DLT window of 6 months and find the maximum tolerated dose. The primary endpoint is unacceptable radiation-induced toxicities (Grade 4, mucositis, dermatitis, or Grade 3 myelopathy, osteoradionecrosis) occurring within 6 months following radiotherapy. The second endpoint is any grade 3 toxicity occurring in 3–6 months after radiation. Discussion: The PIRATES dose-escalation approach is designed to provide a safe avenue to intensify local treatment for HNC patients for whom therapy with conventional radiation dose levels is likely to fail. PIRATES aims to minimize the radiation damage to the tissue surrounding the tumor volume with the combination of proton therapy and adaptive radiotherapy and within the high dose tumor volume with hybrid hyper-fractionation and not boosting mucosal and bone tissues. Ultimately, if successful, PIRATES has the potential to safety increase local control rates in HNC patients with high loco-regional failure risk. Trial registration: ClinicalTrials.gov ID: NCT04870840; Registration date: May 4, 2021. Netherlands Trial Register ID: NL9603; Registration date: July 15, 2021

MR-Guided Stereotactic Radiation Therapy for Head and Neck Cancers

PURPOSE: MR-guided radiotherapy (MRgRT) has the advantage of utilizing high soft tissue contrast imaging to track daily changes in target and critical organs throughout the entire radiation treatment course. Head and neck (HN) stereotactic body radiation therapy (SBRT) has been increasingly used to treat localized lesions within a shorter timeframe. The purpose of this study is to examine the dosimetric difference between the step-and-shot intensity modulated radiation therapy (IMRT) plans on Elekta Unity and our clinical volumetric modulated arc therapy (VMAT) plans on Varian TrueBeam for HN SBRT. METHOD: Fourteen patients treated on TrueBeam sTx with VMAT treatment plans were re-planned in the Monaco treatment planning system for Elekta Unity MR-Linac (MRL). The plan qualities, including target coverage, conformity, homogeneity, nearby critical organ doses, gradient index and low dose bath volume, were compared between VMAT and Monaco IMRT plans. Additionally, we evaluated the Unity adaptive plans of adapt-to-position (ATP) and adapt-to-shape (ATS) workflows using simulated setup errors for five patients and assessed the outcomes of our treated patients. RESULTS: Monaco IMRT plans achieved comparable results to VMAT plans in terms of target coverage, uniformity and homogeneity, with slightly higher target maximum and mean doses. The critical organ doses in Monaco IMRT plans all met clinical goals; however, the mean doses and low dose bath volumes were higher than in VMAT plans. The adaptive plans demonstrated that the ATP workflow may result in degraded target coverage and OAR doses for HN SBRT, while the ATS workflow can maintain the plan quality. CONCLUSION: The use of Monaco treatment planning and online adaptation can achieve dosimetric results comparable to VMAT plans, with the additional benefits of real-time tracking of target volume and nearby critical structures. This offers the potential to treat aggressive and variable tumors in HN SBRT and improve local control and treatment toxicity

Patterns of Failure after IMRT in Head and Neck Squamous Cell Carcinoma of Unknown Primary: Implication of Elective Nodal and Mucosal Dose Coverage

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