Head And Neck Tumor Research Articles

ISA-Net: Improved spatial attention network for PET-CT tumor segmentation

Background and Objective: Achieving accurate and automated tumor segmentation plays an important role in both clinical practice and radiomics research. Segmentation in medicine is now often performed manually by experts, which is a laborious, expensive and error-prone task. Manual annotation relies heavily on the experience and knowledge of these experts. In addition, there is much intra- and interobserver variation. Therefore, it is of great significance to develop a method that can automatically segment tumor target regions. Methods: In this paper, we propose a deep learning segmentation method based on multimodal positron emission tomography-computed tomography (PET-CT), which combines the high sensitivity of PET and the precise anatomical information of CT. We design an improved spatial attention network(ISA-Net) to increase the accuracy of PET or CT in detecting tumors, which uses multi-scale convolution operation to extract feature information and can highlight the tumor region location information and suppress the non-tumor region location information. In addition, our network uses dual-channel inputs in the coding stage and fuses them in the decoding stage, which can take advantage of the differences and complementarities between PET and CT. Results: We validated the proposed ISA-Net method on two clinical datasets, a soft tissue sarcoma(STS) and a head and neck tumor(HECKTOR) dataset, and compared with other attention methods for tumor segmentation. The DSC score of 0.8378 on STS dataset and 0.8076 on HECKTOR dataset show that ISA-Net method achieves better segmentation performance and has better generalization. Conclusions: The method proposed in this paper is based on multi-modal medical image tumor segmentation, which can effectively utilize the difference and complementarity of different modes. The method can also be applied to other multi-modal data or single-modal data by proper adjustment.

Head and neck tumor segmentation in PET/CT: The HECKTOR challenge.

This paper relates the post-analysis of the first edition of the HEad and neCK TumOR (HECKTOR) challenge. This challenge was held as a satellite event of the 23rd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020, and was the first of its kind focusing on lesion segmentation in combined FDG-PET and CT image modalities. The challenge's task is the automatic segmentation of the Gross Tumor Volume (GTV) of Head and Neck (H&N) oropharyngeal primary tumors in FDG-PET/CT images. To this end, the participants were given a training set of 201 cases from four different centers and their methods were tested on a held-out set of 53 cases from a fifth center. The methods were ranked according to the Dice Score Coefficient (DSC) averaged across all test cases. An additional inter-observer agreement study was organized to assess the difficulty of the task from a human perspective. 64 teams registered to the challenge, among which 10 provided a paper detailing their approach. The best method obtained an average DSC of 0.7591, showing a large improvement over our proposed baseline method and the inter-observer agreement, associated with DSCs of 0.6610 and 0.61, respectively. The automatic methods proved to successfully leverage the wealth of metabolic and structural properties of combined PET and CT modalities, significantly outperforming human inter-observer agreement level, semi-automatic thresholding based on PET images as well as other single modality-based methods. This promising performance is one step forward towards large-scale radiomics studies in H&N cancer, obviating the need for error-prone and time-consuming manual delineation of GTVs.

Calpain-2 regulates hypoxia/HIF-induced plasticity toward amoeboid cancer cell migration and metastasis

Hypoxia, through hypoxia inducible factor (HIF), drives cancer cell invasion and metastatic progression invarious cancer types. In epithelial cancer, hypoxia induces the transition to amoeboid cancer cell dissemination, yet the molecular mechanisms, relevance for metastasis, and effective intervention to combat hypoxia-induced amoeboid reprogramming remain unclear. Here, we identify calpain-2 as a key regulator and anti-metastasis target of hypoxia-induced transition from collective to amoeboid dissemination of breast and head and neck (HN) carcinoma cells. Hypoxia-induced amoeboid dissemination occurred through low extracellular matrix (ECM)-adhesive, predominantly bleb-based amoeboid movement, which was maintained by a low-oxidative and -glycolytic energy metabolism ("eco-mode"). Hypoxia induced calpain-2-mediated amoeboid conversion by deactivating β1 integrins through enzymatic cleavage of the focal adhesion adaptor protein talin-1. Consequently, targeted downregulation or pharmacological inhibition of calpain-2 restored talin-1 integrity and β1 integrin engagement and reverted amoeboid to elongated phenotypes under hypoxia. Calpain-2 activity was required for hypoxia-induced amoeboid conversion in the orthotopic mouse dermis and upregulated in invasive HN tumor xenografts invivo, and attenuation of calpain activity prevented hypoxia-induced metastasis to the lungs. This identifies the calpain-2/talin-1/β1 integrin axis as a druggable mechanosignaling program that conserves energy yet enables metastatic dissemination that can be reverted by interfering with calpain activity.

Head and Neck Oropharyngeal GTV Autosegmentation: Combining nnU-Net With Shape Representation Loss Driven by a Variational Autoencoder Model

Autosegmentation models for tumors are becoming increasingly important across several domains. GTV autosegmentations can facilitate faster radiation treatment planning, standardize delineation for radiomics, and provide contour consistency across centers. Oropharyngeal squamous cell carcinomas (SCC) of the head and neck serve as a challenging tumor to segment given the underlying anatomy and imaging characteristics. We build upon nnU-Net, a new medical image segmentation framework that uses a set of heuristics based on the training data type (modality, size etc.) and available resources (GPU RAM etc.) to optimally select pre-processing steps, model parameters and model ensembling techniques. Previous work has shown that latent-space based shape representation (obtained from stacked auto-encoder) of organs at risk within the head and neck, when used in loss function, improves OAR segmentation accuracy. Here, we apply nnU-Net for autosegmentation of oropharyngeal SCCs GTVs. And we adapted nnU-Net to utilize a shape representation loss function to further constrain the GTV segmentations.The 2020 HEad and NeCK TumOR (HECKTOR) Challenge at the MICCAI 2020 conference provided a dataset of 201 patients with oropharyngeal caner with pre-radiation treatment CT and PET images from 4 different medical centers. We applied autosegmentation to this HECKTOR dataset, and we tested on an independent dataset consisting of 53 patients from a fifth and separate institution. We trained a model with the original nnU-Net framework on the HECKTOR CT and PET training data. To generate a shape representation model, we built a variational autoencoder with input as the cropped and centered ground truth GTV binary masks. We performed hyperparameter optimization and found an optimal latent space size of 50, a network depth of 5 convolutional layers, and a KL loss weight of 0.001. To constrain the output of nnU-Net, we computed the L1-loss in the latent space between the ground truth and the autosegmentation, generating a shape representation model (SRM) loss function.The latent space of the variational autoencoder encodes effectively shape information of GTVs, including size and T-staging of the tumor. The original nnU-Net model achieved a 74.7% Dice score on the test set, which placed 3rd in the post-submission HECKTOR challenge. Our SRM model constrained the segmentation and achieved a Dice of 75.9%, which placed first in the post-submission HECKTOR challenge as of February 2021.These results show that nnU-Net can be used to generate a well-performing autosegmentation model for head and neck GTV segmentation using multimodal input. We also demonstrate that the PyTorch framework can be readily altered and optimized for particular tasks. Our shape representation loss was able to improve performance and achieve the top segmentation result in the HECKTOR challenge. Further optimizations into this framework are actively being explored.

Prevalence of odontogenic cysts and tumors on turkish sample according to latest classification of world health organization: A 10-year retrospective study.

The aims of this study are to investigate the prevalence of odontogenic cysts and tumors occurred in a sample of Turkish population in the last 10 years and to compare the data with latest reports. The present retrospective study was carried out at Gazi University, School of Dentistry (GUSD) in Ankara, Turkey. All the data was retrieved from the GUSD archive on patients treated for various oral and maxillofacial lesions between 2008 and 2018. Patients' demographical data, main clinical features of the lesions along with histopathological findings were retrieved from the dental files of the patients. The type of lesions was evaluated according to the latest Head and Neck Tumor (HNT) classification published by the World Health Organization (WHO) in 2017. Data was analyzed by descriptive statistics and Chi-square test using SPSS version 21.0 software. Among a total of 739 biopsy-conducted lesions, 467 (63.19%) were odontogenic cysts, 43 (5.82%) were benign odontogenic tumors, and 7 (0.95%) were malignant tumors. The rest of 222 cases were defined as others. The present study assessed the demographic and clinico-pathological characteristics of odontogenic cysts/tumors in a group of Turkish people, who visited GUSD for therapeutic purpose in the past 10 years. Results showed that male patients in their 5th-6th decades have the highest risk of odontogenic cyst/tumor, especially in the mandibular posterior region.

Diffusion kurtosis imaging in head and neck cancer: A correlation study with dynamic contrast enhanced MRI

PurposeTo investigate the biophysical meaning of Diffusion Kurtosis Imaging (DKI) parameters via correlations with the perfusion parameters obtained from a long Dynamic Contrast Enhanced MRI scan, in head and neck (HN) cancer. MethodsTwenty two patients with newly diagnosed HN tumor were included in the present retrospective study. Some patients had multiple lesions, therefore a total of 26 lesions were analyzed. DKI was acquired using 5b values at 0, 500, 1000,1500 and 2000 s/mm2. DCE-MRI was obtained with 130 dynamic volumes, with a temporal resolution of 5 s, to achieve a long scan time (>10 min). The apparent diffusion coefficient Dapp and apparent diffusional kurtosis Kapp were calculated voxel-by-voxel, removing the point at b value = 0 to eliminate possible perfusion effects on the parameter estimations. The transfer constants Ktrans and Kep, ve, and the histogram-based entropy (En) and interquartile range (IQR) of each DCE-MRI parameter were quantified. Correlations between all variables were investigated by the Spearman’s Rho correlation test. ResultsModerate relationships emerged between Dapp and Kep (Rho = − 0.510, p = 0.009), and between Dapp and ve (Rho = 0.418, p = 0.038). En(Kep) was significantly related to Kapp (Rho = 0.407, p = 0.043), while IQR(Kep) showed an inverse association with Dapp (Rho = -0.422, p = 0.035). ConclusionsA weak to intermediate correlation was found between DKI parameters and both Kep and ve. The kurtosis was associated to the intratumoral heterogeneity and complexity of the capillary permeability, expressed by En(Kep).

Critical Changes in the Staging of Head and Neck Cancer.

The many changes made to the head and neck (HN) chapters of the eighth edition of the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC) cancer staging manuals have resulted in confusion from clinicians and radiologists. These changes have even raised concerns for validity. In prior staging manual updates, the changes made largely provided simplification of more complex staging details. The current eighth edition of the AJCC/UICC staging manuals introduced greater granularity to HN tumor staging. This reflects the current understanding of pathophysiology of these cancers and is necessary to create a more accurate prognosis for these patients. The most commonly encountered example of manual changes is the separate staging of viral-associated oropharyngeal squamous cell carcinoma from tobacco and alcohol use-associated squamous cell carcinoma. While anatomic imaging is critical for HN cancer staging, and frequently outweighs clinical examination, some changes to staging make it impossible for a stage to be assigned until surgical resection is performed. In all, the AJCC/UICC eighth edition changes, the impact on radiologists, and the rationale behind the changes will be discussed. Additionally, opportunities for radiologists to contribute to research that may influence the next edition of AJCC/UICC cancer staging manuals will be proposed. Keywords: Head/Neck, Oncology, Pharynx, Staging © RSNA, 2020.

Diabetes and its Potential Impact on Head and Neck Oncogenesis.

In recent years, the incidence of diabetes mellitus and cancer has increased sharply; indeed, these have become the two most important diseases threatening health and survival. Head and neck (HN) tumors are the sixth most common malignancies in humans. Numerous studies have shown that there are many common risk factors for diabetes mellitus and HN squamous cell carcinoma, including advanced age, poor diet and lifestyle, and environmental factors. However, the mechanism linking the two diseases has not been identified. A number of studies have shown that diabetes affects the development, metastasis, and prognosis of HN cancer, potentially through the associated hyperglycemia, hyperinsulinemia and insulin resistance, or chronic inflammation. More recent studies show that metformin, the first-line drug for the treatment of type 2 diabetes, can significantly reduce the risk of HN tumor development and reduce mortality in diabetic patients. Here, we review recent progress in the study of the relationship between diabetes mellitus and HN carcinogenesis, and its potential mechanisms, in order to provide a scientific basis for the early diagnosis and effective treatment of these diseases.

Head and neck cancer during pregnancy

The incidence of cancer during pregnancy is low but is slightly increasing. Data on incidence and etiology of head and neck (HN) cancers in pregnant women are rare. We evaluated the frequency, tumor type, associated factors, and specific biomarkers in HN cancers occurring in pregnant (and peripartum) women. A systematic literature search was performed on PubMed, for any HN tumor site occurring in pregnant women. Sixty cases of HN cancers occurring during pregnancy were identified. Most of them were oral cavity cancers. Relationships with oncogenic viruses, hormonal disturbance, and shift in maternal immunity profile were identified. Carcinogenesis of HN cancers in pregnant women may be led by different cancer type-specific hallmarks. Relevance of these etiological factors with respect to treatments and birth control recommendations is being investigated by the REFCOR in an ambispective study.

Abstract 3813: Development of JNJ-64164711, a low fucose anti-GITR antibody for enhanced depletion of tumor regulatory T cells (Tregs)

Abstract Background: Checkpoint blockade of PD-1/PDL-1 or CTLA-4 has demonstrated clinical benefit in a subset of cancer patients (pts). To further improve the outcome, approaches to deplete immunosuppressive Tregs are being developed. Emerging evidence supports that the TNF receptor superfamily member 18 (TNFRSF18 or GITR) is highly expressed on intratumoral (i.t.) Tregs with limited expression on effector T cells or circulating immune cells (1,2). This differential expression allows for development of monoclonal antibody (mAb) therapies that eliminate this population while sparing other immune subsets. Herein we characterize JNJ-64164711 (JNJ-711), a fully human anti-GITR mAb being developed to selectively deplete GITR+ Tregs and expand the population of pts that may respond to immunotherapy. Methods: Treg frequency and GITR expression on human cancer specimens was performed by IHC and multicolor flow cytometric analysis (FC). JNJ-711 was assessed for binding to GITR (human and cyno) and human Fcγ receptors, and inhibition of hGITRL binding to hGITR. The JNJ-711 binding epitope was mapped by hydrogen-deuterium exchange. JNJ-711 functional activity was determined by 1) an NF-kB reporter assay, 2) antibody dependent cellular cytotoxicity (ADCC) on GITR+ cell lines, and 3) JNJ-711 mediated Treg depletion in primary pts tumor samples. Results: GITR expression prevalence was evaluated by IHC in multiple solid tumors. Immune cell GITR expression was observed in head and neck (HN), esophageal (ESO), non-small cell lung carcinoma (NSCLC), colorectal (CRC) and prostate cancers. GITR was moderately expressed on HN and ESO tumor cells. GITR expression (by FC) was higher on tumor Tregs versus other T cell populations in the tumor and periphery across NSCLC, CRC, ovarian and renal cell carcinoma samples. GITR was differentially higher on i.t. effector Tregs (eTreg) whereas CCR4 was highest on CD4+ T cells in circulation. JNJ-711 binds to hGITR on cells with high affinity [KD= 180 pM], has a log greater affinity to FcγRIIIa [KD= 37 nM on 158V; KD= 180 nM on 158F], a slower dissociation rate than most GITR agonist (Ag) mAb tested [Koff= 5.47 x 10-4 s-1 for Fab], and binds to the CRD1 of GITR. Unlike other GITR Ag mAbs tested, JNJ-711 does not block GITR interaction with GITRL. JNJ-711 demonstrates higher ADCC mediated cell depletion than other GITR Ag mAbs in clinical development on 1) GITR+ hematologic tumor cell lines (HuT102, KMS-12-BM, RPMI 8226, JJN-3), 2) primary activated GITR+ T cells, and 3) in vitro expanded Tregs. Using dissociated primary pts samples, JNJ-711 selectively depleted i.t. eTregs. Conclusion: JNJ-64164711 selectively depletes hGITR+ cells including Tregs and has potential to enhance antitumor immune response. This antibody is being evaluated for clinical development.

HOTAIRM1 competed endogenously with miR-148a to regulate DLGAP1 in head and neck tumor cells.

This study is aimed to explore the regulatory effect of lncRNA HOTAIR/miR‐148a/DLGAP1 axis on head and neck tumor (HNT) cell growth, cell mobility, and invasiveness. HOTAIRM1, miR‐148a, and DLGAP1 level in HNT tissues and adjacent normal tissues were measured by qRT‐PCR. Cell Counting Kit‐8 (CCK‐8) and Transwell (migration and invasion) assay were used to survey the influence of HOTAIRM1, miR‐148a, and DLGAP1 on Fadu cells. Nude mouse xenograft was utilized to validate the influence of HOTAIRM1 in vivo. Dual‐luciferase reporter assay confirms the relationship between HOTAIRM1 and miR‐148a, miR‐148a, and DLGAP1. The expression level of HOTAIRM1 was downregulated in human HNT tissues and cells. Overexpression of HOTAIRM1 significantly moderated Fadu cells proliferation, apoptosis, migration, and invasion in vitro and impaired the tumorigenesis in vivo. The expression level of miR‐148a was upregulated in human HNT tissue compared to the adjacent tissues. We identified that miR‐148a was a target of HOTAIRM1 and its expression levels were reduced by HOTAIRM1. Transfection of miR‐148a mimics increased proliferation, migration, and invasion of Fadu cells. DLGAP1 was identified as a novel target of miR‐148a and its expression level was promoted by either HOTAIRM1 overexpression or miR‐148a knockdown. Overexpression of DLGAP1 also facilitated the cell viability and metastasis of Fadu cells. HOTAIRM1 was confirmed as a tumor suppressor via sponging miR‐148a and promote the expression of DLGAP1, which could be regarded as an important target for the prevention and treatment of HNT.

Correlation study between DKI and conventional DWI in brain and head and neck tumors

PurposeTo investigate the relationship between the Diffusion Kurtosis Imaging (DKI) parameters and conventional metrics provided by Diffusion-weighted imaging (DWI) in patients affected by Brain or Head and Neck (HN) cancer. MethodsTen patients affected by brain tumor and nine patients with HN tumor underwent a pre-treatment MR examination at 3 T. The largest tumor section was manually contoured by two expert neuroradiologists. The apparent diffusion coefficient (Dapp) and apparent diffusional kurtosis (Kapp) parameters were determined at the voxel level by using the DKI model, and compared to the apparent diffusion coefficient (ADC) and the tissue diffusion coefficient (Dmono) obtained from mono-exponential fitting methods. The Akaike Information Criteria (AIC) was calculated to assess the quality of the fitting methods. Cross-correlations between all the variables were assessed using the Spearman rank test. ResultsIncreased Kapp values were found in each lesion. All parameters were strongly related, in particular an inverse relationship emerged between median values of Kapp and Dapp/Dmono/ADC in both patient groups, while Dapp showed positive correlations with Dmono and ADC. From the analysis at the voxel level, significant inverse associations were found between Kapp and Dmono within the lesions, while a weak or moderate association emerged between Kapp and ADC or Dapp. ConclusionsA significant association between the apparent diffusional kurtosis Kapp and the tissue diffusion coefficient Dmono emerged for both brain and HN tumors at 3 T, suggesting that both variables may consistently reflect deeper insight into the microstructural characteristics of tumors.

Implant Utilization and Time to Prosthetic Rehabilitation in Conventional and Advanced Fibular Free Flap Reconstruction of the Maxilla and Mandible.

Precisely designed jaw reconstruction rehabilitation (JRR) is important to the integrity of the jaw structure and oral functions. Advanced three-dimensional (3D) digital surgical design and simulation (SDS) techniques have the potential to reduce time to reconstructive and dental treatment completion, thereby promoting early functional oral rehabilitation. This study investigated the use of SDS in JRR procedures. A retrospective chart review was conducted on adult head and neck tumor (HNT) participants who completed JRR treatment with a fibular free flap (FFF) reconstruction. Two treatment approaches, advanced 3D SDS technique (with-SDS) and conventional, nondigitally planned technique (without-SDS), included the use of osseointegrated implants. Data were collected from adult patients treated between January 2000 and March 2014 at the Institute for Reconstructive Sciences in Medicine (iRSM). Participants were excluded if they underwent a bone-containing augmentation to the FFF reconstruction. The without-SDS group underwent a conventional, nonguided FFF reconstruction followed by nonguided implant placement. The with-SDS group underwent a guided FFF reconstruction with guided implant placement during the reconstructive surgery. The outcome measures included implant utilization (ratio of implants placed to connected) and time to prosthetic connection after FFF reconstruction. Mann-Whitney U test was used to analyze the data. The digital SDS technique (with-SDS) group completed prosthetic treatment with a significantly higher utilization of implants as well as a significantly shorter time to prosthetic delivery. SDS allows an interdisciplinary treatment team to work together to create a virtual plan that leads to greater efficiency in patient treatment time and utilization of dental implants.

Effective dose estimation for oncological and neurological PET/CT procedures

BackgroundThe aim of this study was to retrospectively evaluate the patient effective dose (ED) for different PET/CT procedures performed with a variety of PET radiopharmaceutical compounds.PET/CT studies of 210 patients were reviewed including Torso (n = 123), Whole body (WB) (n = 36), Head and Neck Tumor (HNT) (n = 10), and Brain (n = 41) protocols with 18FDG (n = 170), 11C-CHOL (n = 10), 18FDOPA (n = 10), 11C-MET (n = 10), and 18F-florbetapir (n = 10). ED was calculated using conversion factors applied to the radiotracer activity and to the CT dose-length product.ResultsTotal ED (mean ± SD) for Torso-11C-CHOL, Torso-18FDG, WB-18FDG, and HNT-18FDG protocols were 13.5 ± 2.2, 16.5 ± 4.5, 20.0 ± 5.6, and 15.4 ± 2.8 mSv, respectively, where CT represented 77, 62, 69, and 63% of the protocol ED, respectively. For 18FDG, 18FDOPA, 11C-MET, and 18F-florbetapir brain PET/CT studies, ED values (mean ± SD) were 6.4 ± 0.6, 4.6 ± 0.4, 5.2 ± 0.5, and 9.1 ± 0.4 mSv, respectively, and the corresponding CT contributions were 11, 14, 23, and 26%, respectively. In 18FDG PET/CT, variations in scan length and arm position produced significant differences in CT ED (p < 0.01). For dual-time-point imaging, the CT ED (mean ± SD) for the delayed scan was 3.8 ± 1.5 mSv.ConclusionsThe mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical.

Evaluation of oral prophylaxis during and after intensity-modulated radiotherapy due to head and neck cancer--a retrospective study.

The aim of this study was to retrospectively analyze the influence of a prophylaxis protocol of head and neck tumor (HNT) patients during and after intensity-modulated radiotherapy (IMRT). In this 5-year retrospective study (2009-2013), 70 (m 55, f 15; age range 28-8 years; median 58.7 years) out of 248 HNT patients of the Clinic of Cranio-Maxillofacial and Oral Surgery at the University of Zurich, Switzerland, fulfilled the inclusion criteria. Parameters of investigation were the salivary flow rates, possible dental foci and the dental status, oral side effects of radiotherapy, the prophylaxis protocol, and patient's compliance to this protocol. The following time points before during and after IMRT (6 weeks) were analyzed: prior to IMRT, 2-4 weeks, 6 weeks and 3, 6, and 12 months after the onset of radiotherapy. Unstimulated salivary flow rate, pH value of unstimulated salivary, and stimulated salivary flow rate showed a significant reduction over time (p < 0.001). One year after IMRT, both unstimulated and stimulated salivary flow showed a statistically significant lower salivary flow. The number of caries-affected sites per patient was significantly higher for patients with low compliance to the prophylaxis protocol (mean: low compliance 1.36, high compliance 0.26). Almost 75% of the evaluated patients suffered immediate gustatory change, and 47.1% showed signs of radiostomatitis through IMRT. High compliance to the prophylaxis protocol during and after radiotherapy is a key factor for the reduction of radiation side effects on dental hard tissue. High compliance to a monitored prophylaxis program is crucial for patients after head and neck surgery.

Analysis of fractionation correction methodologies for multiple phase treatment plans in radiation therapy

Radiation therapy is often delivered by multiple sequential treatment plans. For an accurate radiobiological evaluation of the overall treatment, fractionation corrections to each dose distribution must be applied before summing the three-dimensional dose matrix of each plan since the simpler approach of performing the fractionation correction to the total dose-volume histograms, obtained by the arithmetical sum of the different plans, becomes inaccurate for more heterogeneous dose patterns. In this study, the differences between these two fractionation correction methods, named here as exact (corrected before) and approximate (after summation), respectively, are assessed for different cancer types. Prostate, breast, and head and neck (HN) tumor patients were selected to quantify the differences between two fractionation correction methods (the exact vs the approximate). For each cancer type, two different treatment plans were developed using uniform (CRT) and intensity modulated beams (IMRT), respectively. The responses of the target and normal tissue were calculated using the Poisson linear-quadratic-time model and the relative seriality model, respectively. All treatments were radiobiologically evaluated and compared using the complication-free tumor control probability (P+), the biologically effective uniform dose (D) together with common dosimetric criteria. For the prostate cancer patient, an underestimation of around 14%-15% in P+ was obtained when the fractionation correction was applied after summation compared to the exact approach due to significant biological and dosimetric variations obtained between the two fractionation correction methods in the involved lymph nodes. For the breast cancer patient, an underestimation of around 3%-4% in the maximum dose in the heart was obtained. Despite the dosimetric differences in this organ, no significant variations were obtained in treatment outcome. For the HN tumor patient, an underestimation of about 5% in treatment outcome was obtained for the CRT plan as a result of an underestimation of the planning target volume control probability by about 10%. An underestimation of about 6% in the complication probability of the right parotid was also obtained. For all the other organs at risk, dosimetric differences of up to 4% were obtained but with no significant impact in the expected clinical outcome. However, for the IMRT plan, an overestimation in P+ of 4.3% was obtained mainly due to an underestimation of the complication probability of the left and right parotids (2.9% and 5.8%, respectively). The use of the exact fractionation correction method, which is applying fractionation correction on the separate dose distributions of a multiple phase treatment before their summation was found to have a significant expected clinical impact. For regions of interest that are irradiated with very heterogeneous dose distributions and significantly different doses per fraction in the different treatment phases, the exact fractionation correction method needs to be applied since a significant underestimation of the true patient outcome can be introduced otherwise.

Detection of risk factors that influence weight loss in patients undergoing radiotherapy

AimTo identify risk factors that influence weight loss in patients receiving radiotherapy. BackgroundIt is a well-known fact that cancer patients can be affected by malnutrition at the onset of the disease and during treatment due to the toxicity. Pretreatment weight loss alone does not predict those who will need nutritional supplementation. Instead, a variety of nutritional and tumor related factors needs to be taken into account. Material and methodsA retrospective study was conducted on 129 patients with different tumor locations. Weight loss was evaluated during radiotherapy and one month after treatment. The impact of age, ECOG, chemotherapy, pretreatment weight loss, tumor location, previous surgery and TNM were analyzed. We aimed to identify a high-risk group of patients before starting treatment. ResultsThe average net weight loss during radiotherapy and one month after treatment for this group of patients was 0.68kg and 1.6kg, respectively. Median weight loss during radiotherapy was 2.6 kg for head and neck (HN) patients and 0.27 kg for other tumor sites (p=0.028). Median weight loss one month after radiotherapy was 3.7kg for HN patients and 1.1kg for the rest of the patients (p=0.034). The median weight loss one month after treatment was 3.2 kg for patients receiving chemotherapy and 0.5kg for those patients who did not receive chemotherapy (p<0.001). A regression analysis determined that HN tumor location and the use of chemotherapy were independent risk factors. ConclusionsNutritional status must be monitored and managed before, during and after treatment. A variety of nutritional and tumor-related factors must be considered. According to our results, head and neck tumors and the use of chemotherapy are the only two factors considered statistically significant. Because patients continue to lose weight after treatment, we recommend close surveillance after radiotherapy.

The Clinical Course of Head and Neck Cancer in Patients with Chronic Lymphocytic Leukemia

Abstract 4741 BACKGROUND.Patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing second primary malignancies, including squamous cell cancers (SCC) of the Head and Neck (HNC). While cutaneous SCC have been shown to behave more aggressively in the setting of CLL, little information exists on the clinical course and outcome of SCC of the oral cavity and pharynx. METHODS.The Massachusetts General Hospital Tumor Registry was queried for all patients with ICD-O-3 codes corresponding to both CLL/SLL and HNC from January 1989 to July 2010, returning seventeen patients. The data collected included patient demographics, blood work and cytogenetics (when available) at the time of CLL diagnosis, primary HNC tumor histology and stage, and all pertinent treatment data, including types of treatment and clinical response. Survival was calculated using the Kaplan-Meier method. RESULTS.Seventeen patients had a diagnosis of both CLL and HNC. Of those, three were excluded from the study as treatment data was unavailable. The fourteen remaining included 12 males and 2 females. Eight patients had their CLL diagnosed first, and had a median interval to HNC diagnosis of 80 months (2-210 months; mean 89 months), four had their HNC diagnosed first and had a median interval to CLL of 1 month (1-100 months; mean 26 months), and two patients had concurrent diagnoses. The median age at diagnosis was 58.5 years (CLL) and 64 years (HNC). Nine patients (64%) were former or current smokers, all with at least a 20 pack year smoking history. Seven patients presented with Rai stage 0 CLL, three patients with Rai stage 1, one patient each with Rai stage 2 and 3, and two with unknown presentations. HNC tumor presentations included 3 T1 tumors, 3 T2 tumors, 3 T3 tumors, 2 T4 tumors, and 3 TX tumors. Three patients had HPV assessed in their tumor and all were positive.Out of the fourteen patients, nine (64%) received first-line chemotherapy for their CLL: 4 with chlorambucil, 1 with fludarabine/rituximab (FR), 1 with FR/lenalidomide, 1 with rituximab, and 1 each with cytoxan/vincristine and steroid monotherapy. Eight patients received second line therapy, three received third line therapy and one received 7 lines of therapy. Six patients (43%) received chemotherapy and radiation as their primary treatment for their Head and Neck tumor, three (21%) received surgery and radiation, three (21%) received only radiation, one received surgery, and one received radiation, chemotherapy, and surgery. One patient required hospitalization due to neutropenic fever during their radiation treatment, and one patient had a week of chemotherapy withheld due to leukopenia, but both were able to complete their full course of therapy. Three patients (21%) received chemotherapy for their CLL before any HNC treatment. These three patients were able to tolerate full HNC therapy without infectious complications or unanticipated cytopenias.First-line therapy for HNC had a median progression-free survival of 26.9 months (range 10.7 – 145.2 months; 95% CI, 12 to 42 months) and a median overall survival of 45.1 months (range 1 to 256.1 months; 95% CI, 9 to 81 months). The median overall survival from HNC for treated CLL patients was 22.6 months and for untreated 59.2 months (p= 0.596). Five patients died from their HNC (36%), two patients died from their CLL (14%), two patients died from unrelated causes, and five patients remain in remission. There were no significant differences in HNC presentation or survival between treated and untreated CLL. CONCLUSIONS.Prior or concurrent CLL therapy did not affect HNC treatment or induce any unexpected toxicities. Interestingly, seven out of fourteen patients (including 2 out of 3 HPV positive) were diagnosed with HNC within 6 months of CLL diagnosis, suggesting that the risk of secondary malignancies may be independent of the degree of immunosuppression attributable to progressive CLL or its therapy. This hypothesis should be explored in a larger population. Disclosures:No relevant conflicts of interest to declare.

A specific approach for elderly patients with head and neck cancer

Approximately 10% of head and neck (HN) tumors occur in patients aged more than or equal to 80 years. In this population, the main challenge for physicians is to deal with the benefit/risk ratio of treatments and tumor-related symptoms. As elderly patients are generally excluded from clinical trials, there is a lack of evidence-based data with regard to the most appropriate multidisciplinary management. The prevalence of frailty and the pattern of comorbidities in this specific population are still unknown. The management of these tumors in a geriatric context is complex due to the high risk of toxicity of locoregional treatments. Thus, physicians often have to adapt to the treatment schedule to decrease potential adverse effects even with a risk of undertreatment. A retrospective series reported that the treatment delivered to elderly patients presenting with HN tumor complies with an institution's policy in less than 50% of cases, emphasizing the need to assess the outcome of personalized/adapted treatment in geriatric patients. The major issue is to determine which adaptation could be carried out, and then, what could be the respective individual benefit/risk ratio of each adaptation. In this review, we will focus on the locoregional management of elderly patients, and develop the issue of adapted local treatment. We will discuss the feasibility of adapted surgery and radiotherapy and provide current evidence-based data that may allow physicians involved in locoregional treatment of elderly patients with HN cancers to be acquainted with practical guidelines. Then, we will highlight the importance of nutritional support in this population in which the prevalence of malnutrition is high.

TH-D-304A-08: Quantitative PET Imaging of Heterogeneous Tumors: The Influence of Patient Position On Recovered Activity

Purpose: Dose‐painting will require precise quantification of uptake within sub‐regions of heterogeneous tumors. We have measured and characterized the effect of patient positioning on heterogeneity within PET images for 2D and 3D acquisition. Methods and Materials: Position‐dependent variations in recovery coefficients (RC) were measured on a multi‐slice PET imaging system using a phantom of five P 18P F‐filled spheres: two10mm and 15mm diameter, one 5mm. Spheres of each size were repositioned in 1mm increments between acquisitions while two kept stationary. 2D and 3D coincident counts were acquired at 4 minutes‐per‐position, and images generated with iterative reconstruction protocols. Measured RC variations were used to calculate expected SUV changes within heterogeneous tumors, for patient positions sampled from distributions of axial, radial, and angular uncertainties associated with head and neck (HN) cancer.Results: For sub‐voxel shifts in axial direction, the peak‐to‐trough RC values (RCBPTB) in 2D mode were 41%, 8% for 5mm and 10mm diameter sub‐regions. In 3D mode, these axial RCBPTB values were 24% and 7%. RCBPTB for radial shifts were 31% and 14% for images acquired in 2D mode, and 37% and 12% for 3D acquisition. All RCBPTB for15mm spheres were within the noise background, as determined from measurements of the stationary spheres.Random adjustments of head position resulted in notable changes in visual appearance and spatial distribution within PET images. For a very heterogeneous HN tumor, estimated population correlation coefficient between images was 0.8 (n = 1000 images × 696 voxels). However, correlation between individual images ranged from 1.0 to 0.6. Conclusion: Reproducibility is necessary for quantitative PET imaging; stable and precise voxel values will result in reliable voxel‐based image analysis. However, sub‐voxel verification of position of tumor sub‐regions is impossible, so shift‐interpolated images, which correspond to more reproducible mean RC values, could potentially reduce this systematic uncertainty.