Background
Cisplatin and cetuximab are both systemic therapies commonly used in combination with radiation (RT) for the definitive treatment of head and neck cancers, but their comparative efficacy ...is unclear.
Methods
Patients with locoregionally advanced (American Joint Committee on Cancer stage III‐IVB) squamous cell carcinomas of the oropharynx, larynx, or hypopharynx were identified in the Surveillance, Epidemiology, and End Results‐Medicare database. Patients received either cisplatin or cetuximab concurrent with RT, as determined by Medicare claims. The primary study outcome was head and neck cancer‐specific mortality (CSM) analyzed with competing risks. Filtering, propensity score matching, and multivariable Fine‐Gray regression were used to adjust for differences between the cisplatin and cetuximab cohorts, including age, comorbidity, and cycles of systemic therapy received.
Results
The total cohort consisted of 1395 patients, of whom 786 (56%) received cisplatin and 609 (44%) received cetuximab; the median follow‐up was 3.5 years in the patients who remained alive. In the cetuximab cohort, CSM was significantly higher than in the cisplatin cohort (39% vs 25% at 3 years; P < .0001). In the matched cohorts (n = 414), the adjusted hazard ratio of CSM for cetuximab was 1.65 (95% confidence interval, 1.30‐2.09; P < .0001) relative to cisplatin, corresponding to an absolute difference of approximately 10% in both CSM and overall survival at 3 years. Cetuximab was associated with less dysphagia, more dermatitis, and a similar incidence of mucositis.
Conclusions
In this sizeable, national patient population, treatment with cetuximab was associated with significantly higher CSM than cisplatin. These results suggest that cisplatin may be the preferred chemotherapeutic agent in this setting.
Both cisplatin and cetuximab are systemic therapies commonly used in combination with radiation for the definitive treatment of head and neck cancers, but their comparative efficacy is unclear. In this population‐based analysis, treatment with cetuximab is associated with higher cancer‐specific mortality than cisplatin, suggesting that cisplatin may be the preferred chemotherapeutic agent in this setting.
In radiation treatment planning, the esophagus is an important organ-at-risk that should be spared in patients with head and neck cancer or thoracic cancer who undergo intensity-modulated radiation ...therapy. However, automatic segmentation of the esophagus from CT scans is extremely challenging because of the structure's inconsistent intensity, low contrast against the surrounding tissues, complex and variable shape and location, and random air bubbles. The goal of this study is to develop an online atlas selection approach to choose a subset of optimal atlases for multi-atlas segmentation to the delineate esophagus automatically. We performed atlas selection in two phases. In the first phase, we used the correlation coefficient of the image content in a cubic region between each atlas and the new image to evaluate their similarity and to rank the atlases in an atlas pool. A subset of atlases based on this ranking was selected, and deformable image registration was performed to generate deformed contours and deformed images in the new image space. In the second phase of atlas selection, we used Kullback-Leibler divergence to measure the similarity of local-intensity histograms between the new image and each of the deformed images, and the measurements were used to rank the previously selected atlases. Deformed contours were overlapped sequentially, from the most to the least similar, and the overlap ratio was examined. We further identified a subset of optimal atlases by analyzing the variation of the overlap ratio versus the number of atlases. The deformed contours from these optimal atlases were fused together using a modified simultaneous truth and performance level estimation algorithm to produce the final segmentation. The approach was validated with promising results using both internal data sets (21 head and neck cancer patients and 15 thoracic cancer patients) and external data sets (30 thoracic patients).
Volumetric-modulated arc therapy (VMAT) is a widely accepted treatment method for head and neck (HN) and cervical cancers; however, creating contours and plan optimization for VMAT plans is a ...time-consuming process. Our group has created an automated treatment planning tool, the Radiation Planning Assistant (RPA), that uses deep learning models to generate organs at risk (OARs), planning structures and automates plan optimization. This study quantitatively evaluates the quality of contours generated by the RPA tool.
For patients with HN (54) and cervical (39) cancers, we retrospectively generated autoplans using the RPA. Autoplans were generated using deep-learning and RapidPlan models developed in-house. The autoplans were, then, applied to the original, physician-drawn contours, which were used as a ground truth (GT) to compare with the autocontours (RPA). Using a "two one-sided tests" (TOST) procedure, we evaluated whether the autocontour normal tissue dose was equivalent to that of the ground truth by a margin, δ, that we determined based on clinical judgement. We also calculated the number of plans that met established clinically accepted dosimetric criteria.
For HN plans, 91.8% and 91.7% of structures met dosimetric criteria for automatic and manual contours, respectively; for cervical plans, 95.6% and 95.7% of structures met dosimetric criteria for automatic and manual contours, respectively. Autocontours were equivalent to the ground truth for 71% and 75% of common DVH metrics for the HN and cervix, respectively.
This study shows that dosimetrically equivalent normal tissue contours can be created for HN and cervical cancers using deep learning techniques. In general, differences between the contours did not affect the passing or failing of clinical dose tolerances.
Unilateral radiotherapy for the treatment of tonsil cancer Chronowski, Gregory M; Garden, Adam S; Morrison, William H ...
International journal of radiation oncology, biology, physics,
05/2012, Letnik:
83, Številka:
1
Journal Article
Recenzirano
To assess, through a retrospective review, clinical outcomes of patients with squamous cell carcinoma of the tonsil treated at the M. D. Anderson Cancer Center with unilateral radiotherapy techniques ...that irradiate the involved tonsil region and ipsilateral neck only.
Of 901 patients with newly diagnosed squamous cell carcinoma of the tonsil treated with radiotherapy at our institution, we identified 102 that were treated using unilateral radiotherapy techniques. All patients had their primary site of disease restricted to the tonsillar fossa or anterior pillar, with <1 cm involvement of the soft palate. Patients had TX (n = 17 patients), T1 (n = 52), or T2 (n = 33) disease, with Nx (n = 3), N0 (n = 33), N1 (n = 23), N2a (n = 21), or N2b (n = 22) neck disease.
Sixty-one patients (60%) underwent diagnostic tonsillectomy before radiotherapy. Twenty-seven patients (26%) underwent excision of a cervical lymph node or neck dissection before radiotherapy. Median follow-up for surviving patients was 38 months. Locoregional control at the primary site and ipsilateral neck was 100%. Two patients experienced contralateral nodal recurrence (2%). The 5-year overall survival and disease-free survival rates were 95% and 96%, respectively. The 5-year freedom from contralateral nodal recurrence rate was 96%. Nine patients required feeding tubes during therapy. Of the 2 patients with contralateral recurrence, 1 experienced an isolated neck recurrence and was salvaged with contralateral neck dissection only and remains alive and free of disease. The other patient presented with a contralateral base of tongue tumor and involved cervical lymph node, which may have represented a second primary tumor, and died of disease.
Unilateral radiotherapy for patients with TX-T2, N0-N2b primary tonsil carcinoma results in high rates of disease control, with low rates of contralateral nodal failure and a low incidence of acute toxicity requiring gastrostomy.
The primary cause of death due to head and neck squamous cell carcinoma (HNSCC) is local treatment failure. The goal of this study was to examine this phenomenon using an unbiased approach.
We ...utilized human papilloma virus (HPV)-negative cell lines rendered radiation-resistant (RR) via repeated exposure to radiation, a panel of HPV-negative HNSCC cell lines and three cohorts of HPV-negative HNSCC tumors (
= 68, 97, and 114) from patients treated with radiotherapy and subjected to genomic, transcriptomic, and proteomic analysis.
RR cell lines exhibited upregulation of several proteins compared with controls, including increased activation of Axl and PI3 kinase signaling as well as increased expression of PD-L1. Additionally, inhibition of either Axl or PI3 kinase led to decreased PD-L1 expression. When clinical samples were subjected to RPPA and mRNA expression analysis, PD-L1 was correlated with both Axl and PI3K signaling as well as dramatically associated with local failure following radiotherapy. This finding was confirmed examining a third cohort using immunohistochemistry. Indeed, tumors with high expression of PD-L1 had failure rates following radiotherapy of 60%, 70%, and 50% compared with 20%, 25%, and 20% in the PD-L1-low expression group (
= 0.01, 1.9 × 10
, and 9 × 10
, respectively). This finding remained significant on multivariate analysis in all groups. Additionally, patients with PD-L1 low/CD8
tumor-infiltrating lymphocytes high had no local failure or death due to disease (
= 5 × 10
and
= 4 × 10
, respectively).
Taken together, our data point to a targetable Axl-PI3 kinase-PD-L1 axis that is highly associated with radiation resistance.
.
•Prolongation of the radiation course increased the hazard of death by 2% per day.•Prolongation >8 days was especially deleterious, while 1–3 days was not adverse.•Use of systemic therapy increased ...the risk of prolongation by 2-fold.•High facility volume (top quartile) decreased the risk of prolongation by 2-fold.•Other predictors included race, insurance status, comorbidity, and stage.
To quantify the survival impact of prolongation of definitive radiotherapy (RT) for head and neck cancer in a national, modern cohort, and to identify predictive factors for prolongation.
The National Cancer Database was queried for adults with non-metastatic cancer of the nasopharynx, oropharynx, larynx, or hypopharynx diagnosed 2004–2015, treated with definitive RT to 66–70 Gy in 30–35 fractions at 2–2.2 Gy per fraction. Multivariable Cox regression and propensity score matching were used to model the survival impact of RT prolongation, adjusting for potential confounders such as age and comorbidity. Predictors of RT prolongation were identified using multivariable multinomial logistic regression.
In total, 36,367 patients were identified. As a continuous variable, RT prolongation increased the relative hazard of death by 2% per day (P < .0001). In the matched cohorts, patients with short (4–8 days) or long prolongation (>8 days) had lower absolute 4-year overall survival by 4% and 12%, respectively (P < .0001), while prolongation of 1–3 days was not significantly adverse. Major predictors of increased risk of prolongation were administration of systemic therapy, baseline comorbidity, lack of private insurance, and tumor/nodal stage. Conversely, higher facility volume was significantly protective, with a 55% lower risk of long prolongation within the topmost quartile (>11.5 patients/year).
RT prolongation, especially >8 days, is significantly deleterious. Systemic therapy and facility volume were major predictors. Early identification of patients at increased risk of treatment interruptions may facilitate implementation of preventive measures.
Purpose:
To develop an automatic segmentation algorithm integrating imaging information from computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) to ...delineate target volume in head and neck cancer radiotherapy.
Methods:
Eleven patients with unresectable disease at the tonsil or base of tongue who underwent MRI, CT, and PET/CT within two months before the start of radiotherapy or chemoradiotherapy were recruited for the study. For each patient, PET/CT and T1‐weighted contrast MRI scans were first registered to the planning CT using deformable and rigid registration, respectively, to resample the PET and magnetic resonance (MR) images to the planning CT space. A binary mask was manually defined to identify the tumor area. The resampled PET and MR images, the planning CT image, and the binary mask were fed into the automatic segmentation algorithm for target delineation. The algorithm was based on a multichannel Gaussian mixture model and solved using an expectation–maximization algorithm with Markov random fields. To evaluate the algorithm, we compared the multichannel autosegmentation with an autosegmentation method using only PET images. The physician‐defined gross tumor volume (GTV) was used as the “ground truth” for quantitative evaluation.
Results:
The median multichannel segmented GTV of the primary tumor was 15.7 cm3 (range, 6.6–44.3 cm3), while the PET segmented GTV was 10.2 cm3 (range, 2.8–45.1 cm3). The median physician‐defined GTV was 22.1 cm3 (range, 4.2–38.4 cm3). The median difference between the multichannel segmented and physician‐defined GTVs was −10.7%, not showing a statistically significant difference (p‐value = 0.43). However, the median difference between the PET segmented and physician‐defined GTVs was −19.2%, showing a statistically significant difference (p‐value =0.0037). The median Dice similarity coefficient between the multichannel segmented and physician‐defined GTVs was 0.75 (range, 0.55–0.84), and the median sensitivity and positive predictive value between them were 0.76 and 0.81, respectively.
Conclusions:
The authors developed an automated multimodality segmentation algorithm for tumor volume delineation and validated this algorithm for head and neck cancer radiotherapy. The multichannel segmented GTV agreed well with the physician‐defined GTV. The authors expect that their algorithm will improve the accuracy and consistency in target definition for radiotherapy.
Endoscopic examinations are frequently-used procedures for patients with head and neck cancer undergoing radiotherapy, but radiation treatment plans are created on computed tomography (CT) scans. ...Image registration between endoscopic video and CT could be used to improve treatment planning and analysis of radiation-related normal tissue toxicity. The purpose of this study was to explore the feasibility of endoscopy-CT image registration without prospective physical tracking of the endoscope during the examination.
A novel registration technique called Location Search was developed. This technique uses physical constraints on the endoscope's view direction to search for the virtual endoscope coordinates that maximize the similarity between the endoscopic video frame and the virtual endoscopic image. Its performance was tested on phantom and patient images and compared to an established registration technique, Frame-To-Frame Tracking.
In phantoms, Location Search had average registration errors of 0.55 ± 0.60 cm for point measurements and 0.29 ± 0.15 cm for object surface measurements. Frame-To-Frame Tracking achieved similar results on some frames, but it failed on others due to the virtual endoscope becoming lost. This weakness was more pronounced in patients, where Frame-To-Frame tracking could not make it through the nasal cavity. On successful patient video frames, Location Search was able to find endoscope positions with an average distance of 0.98 ± 0.53 cm away from the ground truth positions. However, it failed on many frames due to false similarity matches caused by anatomical structural differences between the endoscopic video and the virtual endoscopic images.
Endoscopy-CT image registration without prospective physical tracking of the endoscope is possible, but more development is required to achieve an accuracy suitable for clinical translation.
CTV Guidance for Head and Neck Cancers Beadle, Beth M; Anderson, Carryn M
International journal of radiation oncology, biology, physics,
03/2018, Letnik:
100, Številka:
4
Journal Article
Purpose
Breast cancer is the most common cancer in women globally and radiation therapy is a cornerstone of its treatment. However, there is an enormous shortage of radiotherapy staff, especially in ...low‐ and middle‐income countries. This shortage could be ameliorated through increased automation in the radiation treatment planning process, which may reduce the workload on radiotherapy staff and improve efficiency in preparing radiotherapy treatments for patients. To this end, we sought to create an automated treatment planning tool for postmastectomy radiotherapy (PMRT).
Methods
Algorithms to automate every step of PMRT planning were developed and integrated into a commercial treatment planning system. The only required inputs for automated PMRT planning are a planning computed tomography scan, a plan directive, and selection of the inferior border of the tangential fields. With no other human input, the planning tool automatically creates a treatment plan and presents it for review. The major automated steps are (a) segmentation of relevant structures (targets, normal tissues, and other planning structures), (b) setup of the beams (tangential fields matched with a supraclavicular field), and (c) optimization of the dose distribution by using a mix of high‐ and low‐energy photon beams and field‐in‐field modulation for the tangential fields. This automated PMRT planning tool was tested with ten computed tomography scans of patients with breast cancer who had received irradiation of the left chest wall. These plans were assessed quantitatively using their dose distributions and were reviewed by two physicians who rated them on a three‐tiered scale: use as is, minor changes, or major changes. The accuracy of the automated segmentation of the heart and ipsilateral lung was also assessed. Finally, a plan quality verification tool was tested to alert the user to any possible deviations in the quality of the automatically created treatment plans.
Results
The automatically created PMRT plans met the acceptable dose objectives, including target coverage, maximum plan dose, and dose to organs at risk, for all but one patient for whom the heart objectives were exceeded. Physicians accepted 50% of the treatment plans as is and required only minor changes for the remaining 50%, which included the one patient whose plan had a high heart dose. Furthermore, the automatically segmented contours of the heart and ipsilateral lung agreed well with manually edited contours. Finally, the automated plan quality verification tool detected 92% of the changes requested by physicians in this review.
Conclusions
We developed a new tool for automatically planning PMRT for breast cancer, including irradiation of the chest wall and ipsilateral lymph nodes (supraclavicular and level III axillary). In this initial testing, we found that the plans created by this tool are clinically viable, and the tool can alert the user to possible deviations in plan quality. The next step is to subject this tool to prospective testing, in which automatically planned treatments will be compared with manually planned treatments.
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