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Cancer Library VR Case Study Series

Malignant fibrous histiocytoma

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Malignant fibrous histiocytoma

Now referred to as undifferentiated pleomorphic sarcoma

The following case study is inspired by patient data taken directly from the Soft-tissue-Sarcoma Collection within The Cancer Imaging Archive (TCIA), a service that hosts an archive of publicly accessible de-identified cancer medical images.

Case snapshot
  • Name: Bernie Saxophone
  • Gender: M
  • Age: 49
  • Cancer: Sarcoma
  • Type: Soft tissue sarcoma (STS)
  • Histology: Malignant fibrous histiocytoma
  • Grade: High
  • Site of primary STS: Right thigh
  • Treatment: Surgery + radiotherapy + chemotherapy
  • Outcome: Metastasis to lung
Patient introduction

Bernie is a 49 year old man who noticed as he was walking up the stairs a dull aching pain in his right thigh. When he reached the top of the stairs, he saw that part of his right thigh was swollen and recalled that he had in fact bumped his right leg into the kitchen table a few days ago. He read some advice columns online that for muscle strain-like pain, icing the affected area would help. He did this for a couple days, but the tenderness did not go away. After five weeks, his wife brought to Bernie’s attention that not only was the mass still there, but had enlarged noticeably. After some persistent nagging from the wife, he finally made a trip to the doctor’s office.

Clinical assessment

At the doctor’s office, Bernie insisted that the enlarging lump was due to his injury over the kitchen table, and that over time the affected area would naturally heal on its own. The physician was not convinced after observing the rather large mass in his right thigh, and asked Bernie a few standard questions based on his complaints:

 

Physician: When did the pain start?

Bernie: About five weeks ago after bumping into the corner of the kitchen table.

 

Physician: Whendid you first notice this mass?

Bernie: While climbing a set of stairs, maybe a few days afterbumping into the kitchen table.

 

Physician: Has the mass been increasing in size?

Bernie: Yes, it does seem bigger than before.

 

Physician: Is the pain getting worse?

Bernie: Yes, but it’s probably part of the healing process. I’m not concerned.

 

Physician: Have you taken any medication for this?

Bernie: Occasionally a pain reliever here and there. I made sure to ice the area like articles on the Internet instructed.

 

With these answers and information gathered from the patient history, Bernie’s physician ordered a set of imaging tests including an X-ray, magnetic resonance (MR), computed tomography (CT) and positron emission tomography (PET) scans for better visualization of the right thigh. A biopsy was also arranged to extract tissue from the enlarged area on the thigh to evaluate whether there was cancerous activity, and if so, the aggressiveness of the tumor, i.e., pace of spread or tendency to recur.

The pathology report returned with a histology finding of high grade malignant fibrous histiocytoma, now referred to as undifferentiated pleomorphic sarcoma, on the right thigh. Taking into account all information collected, the physician concluded that the mass in Bernie’s right thigh was not swollen due to injury, but soft tissue sarcoma.

It is not uncommon for patients with this particular type of soft tissue sarcoma, particularly malignant fibrous histiocytoma, to assume that a newly formed lump was caused by a physical accident such as bumping into a table or a sharp corner. However, trauma is not known to cause malignant fibrous histiocytoma.1 Some patients with malignant fibrous histiocytoma also incorrectly assume that a swollen mass on the body, such as on the leg, is caused by muscle strain. The physician explained that the tenderness in Bernie’s leg following the kitchen table injury was coincidental with progression of his soft tissue sarcoma, and along those lines, icing the affected area would not have helped.

Grade:

The tumor grade describes a tumor based on how its cells appear under a microscope and gives an indication of the tumor’s aggressiveness, i.e., how quickly the tumor is likely to grow and spread. The grade can help to guide practitioners in making treatment decisions.

    • High grade tumors tend to be more aggressive and thus have higher tendency to recur and spread
    • Low grade tumors tend to be less aggressive and thus have lower tendency to recur and spread2
Soft tissue sarcoma

Soft tissue sarcoma is a group of cancers that forms in soft tissues of the body, such as muscle, fat, nerves, blood vessels, lymph vessels, fibrous tissues, tendons and the lining of joints.3 These sarcomas which are rare and constitute less than 1% of all cancer cases can begin in any part of the body, with the most common primary sites including the arms or legs (60%), torso or abdomen (30%), and head and neck (10%).4 For metastatic soft tissue sarcoma, the most common site of metastasis is the lungs. There are more than 50 histologic types of soft tissue sarcomas, with the more common types including malignant fibrous histiocytoma (more recently called “undifferentiated pleomorphic sarcoma”), liposarcoma, and leiomyosarcoma.5 While the most common treatment involves surgical removal, depending on the size, type, location and aggressiveness of the tumor, radiation and chemotherapy may also be recommended.

Malignant Fibrous Histiocytoma

Malignant fibrous histiocytoma, also referred to as undifferentiated pleomorphic sarcoma, is an aggressive tumor considered in many studies as the most common type of soft tissue sarcoma, accounting for 25-40% of all adult soft tissue sarcoma cases6, though some more current studies rank it as the fourth most common soft tissue sarcoma7.

Following the site distribution trend found for soft tissue sarcoma in general, common sites of involvement for malignant fibrous histiocytoma, particularly of localization on the body regions is as follows: greater than 70% of cases located in the extremities (50% of cases in lower extremities and 25% in upper extremities), 15% of cases in the retroperitoneum, and 3-10% of cases in the head and neck region.8

Individuals with malignant fibrous histiocytoma often complain of a mass or lump, such as a lump on the thigh, that occurred over a short period of time (usually over the course of weeks to months). The mass is also usually found to have enlarged over time. Some patients mistake the lump to be caused by some sort of trauma to the affected area, such as an injury caused by “running into the corner of a table.”9

* The image of the legs (with emphasis on the right thigh) is taken from the BodyMap VR application.

Bernie has many characteristics consistent with the profile of an individual with soft tissue sarcoma of the malignant fibrous histiocytoma histological type: he is male, Caucasian, middle-aged, and presents with a tumor in the lower extremity. His clinical presentation of a mass in the affected area being rapidly enlarging also resembles that of an individual with malignant fibrous histiocytoma. More details on these characteristics:

  • Male: there is a slight male predilection for malignant fibrous histiocytoma with a male-to-female ratio of 1.2:110
  • Caucasian: malignant fibrous histiocytoma is more common in the Caucasian race11
  • Age: some reports state that malignant fibrous histiocytoma tends to arise most frequently during the sixth and seventh decades of life12 while others suggest this average range is younger at 50 to 70 years of age13. There is also literature suggesting that the range falls between 32 to 80 with a mean age of 59 at diagnosis14.
  • Extremities: over 70% of malignant fibrous histiocytoma cases are located in the extremities, with 50% in the lower extremities15

Presentation:

Malignant fibrous histiocytoma presents as a rapidly enlarging mass, with reports of dull aching pain or tenderness from 30% of patients. Some patients complain of trauma to the affected area, hematoma, or muscle strain, but in actuality, trauma does not cause malignant fibrous histiocytoma, and systemic symptoms are not typically expected.16

Treatment planning

After evaluating Bernie’s symptoms and results from diagnostic tests and scans, Bernie’s multidisciplinary healthcare team formulated a plan integrating treatment modalities including surgery, irradiation, and systemic therapy.

Surgery

Surgical management is the cornerstone of treatment for malignant fibrous histiocytoma.16,17 The aim of surgery is to achieve wide surgical resection with clear resection margins.18 In some cases,

Wide surgical resection:

With wide excision, the surgeon cuts out the tumor area with a wide margin to make sure that only healthy tissue remains. A “wide” surgical margin suggests there is a considerable distance between the tumor and the cut, whereas that distance is much less with a “narrow” surgical margin.19 In other words, if the excision does not achieve wide margins around the abnormal tissue, then some of the disease may be left behind.

amputation may be required to ensure that the lesion is completely removed.

Radiotherapy

Radiotherapy is often recommended as a supplement to surgery, and is useful in malignant fibrous histiocytoma cases where the tumor is classified as high-grade, large, deep-seated, affecting the extremities, and where negative (“clean”) margins are not obtained.20,21

Radiation therapy is administered by a radiation oncologist to minimize probability of local recurrence and metastasis of the cancer. The radiation dose typically ranges from 40 Gy to 65 Gy and depends on how much of the tumor was completely removed by surgical treatment and whether there are residual microscopic or macroscopic tumor cells.22

The Cancer Library VR in-app view above shows a snapshot of Bernie’s soft tissue sarcoma of malignant fibrous histiocytoma histological subtype in the right thigh with tumor segmentation displaying the general area to which radiotherapy treatment would be targeted. Cancer Library VR app users can select the segmentations they wish to visualize alongside other anatomical structures. The image is taken from the Cancer Library VR, and contains de-identified patient image and clinical data obtained from The Cancer Imaging Archive (TCIA), Soft-tissue-Sarcoma Collection (TCIA subject ID: STS_021).

Chemotherapy

Post-operative chemotherapy was indicated as part of Bernie’s treatment plan in order to minimize chances of recurrence. Treatment protocol is dependent on size of the primary lesion, whether metastasis is present, and patient age, to name a few factors.23

The role of chemotherapy in treatment of malignant fibrous histiocytoma or even soft tissue sarcoma in general is not clearly understood. Studies have shown only a modest improvement of less than 10% in overall survival  for soft tissue sarcoma patients from the addition of chemotherapy as a treatment modality, though this percentage was higher in individuals with tumors in the extremities as opposed to those with axial or retroperitoneal tumors.24

Follow-up

After completing the series of treatments, Bernie returned to his life and went about his normal routine. During a follow-up session with his physician two years later, it was discovered that the original tumor had spread beyond the initial site of the right thigh. The cancer had metastasized to his lungs.

While this was upsetting news, Bernie was fully aware of this possibility as his physician had already forewarned him when explaining the different treatment options that metastasis was a likely outcome given his initial diagnosis and test results. Bernie’s malignant fibrous histiocytoma was designated as high grade at diagnosis, and studies indicate that most malignant fibrous histiocytomas are high grade, aggressive in biological behavior, and frequently metastasize despite aggressive treatment.25 It is estimated that 35% to 45% of these patients will develop metastasis.

In fact, studies show that not only is distant metastasis common with malignant fibrous histiocytoma, but the most common site of metastasis in individuals with malignant fibrous histiocytoma is the lungs.26

Even though Bernie was unable to achieve disease-free status, he is thankful to be alive given the statistics provided to him by his physician that overall 5-year survival of individuals with malignant fibrous histiocytoma is between 25-70%.27

Bernie is currently receiving treatment for his condition which has progressed from malignant fibrous histiocytoma to include cancer that is metastatic to the lung. His words of advice to anyone facing a similar situation would be to seek medical attention as soon as something feels “off” or perhaps more than just coincidental. Getting something as unsuspecting as a lump on the leg checked out may just save a life.

References
  1. http://sarcomahelp.org/mfh.html
  2. https://www.ncbi.nlm.nih.gov/books/NBK65773/
  3. https://www.cancer.net/cancer-types/sarcoma-soft-tissue/introduction
  4. https://www.cancer.org/cancer/soft-tissue-sarcoma/about/key-statistics.html
  5. https://radiopaedia.org/articles/undifferentiated-pleomorphic-sarcoma-1
  6. https://meddocsonline.org/journal-of-case-reports-and-medical-images/Undifferentiated-pleomorphic-sarcomas-of-the-proximal-femur-A-case-study.pdf
  7. https://www.researchgate.net/publication/325111157_Malignant_fibrous_histiocytoma_of_the_right_upper_leg_-_A_case_report
  8. http://www.tumorsurgery.org/tumor-education/soft-tissue-tumors/soft-tissue-tumor-types/malignant-fibrous-histiocytoma-mfh-undifferentia.aspx
  9. https://radiopaedia.org/articles/undifferentiated-pleomorphic-sarcoma-1?lang=us
  10. https://www.sciencedirect.com/topics/medicine-and-dentistry/malignant-fibrous-histiocytoma
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671031/
  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751900/
    https://en.wikipedia.org/wiki/Resection_margin
  13. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2023
  14. https://www.cancernetwork.com/view/soft-tissue-sarcomas

Special acknowledgement to the researchers and institutions that provided the Soft-tissue-Sarcoma collection datasets on TCIA:

Data Citation

Vallières, Martin, Freeman, Carolyn R., Skamene, Sonia R., & El Naqa, Issam. (2015). A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities. The Cancer Imaging Archive. http://doi.org/10.7937/K9/TCIA.2015.7GO2GSKS

Publication Citation

Vallières, M., Freeman, C. R., Skamene, S. R., & Naqa, I. El. (2015, June 29). A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities. Physics in Medicine and Biology. IOP Publishing. http://doi.org/10.1088/0031-9155/60/14/5471

TCIA Citation

Clark K, Vendt B, Smith K, Freymann J, Kirby J, Koppel P, Moore S, Phillips S, Maffitt D, Pringle M, Tarbox L, Prior F. The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository, Journal of Digital Imaging, Volume 26, Number 6, December, 2013, pp 1045-1057.

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Cancer Library VR Case Study Series

HPV-positive oropharyngeal squamous cell carcinoma

Blog > Cancer Library VR Case Study Series

HPV-positive oropharyngeal squamous cell carcinoma

The following case study is inspired by patient data taken directly from the HNSCC Collection within The Cancer Imaging Archive (TCIA), a service that hosts an archive of publicly accessible de-identified cancer medical images.

Case snapshot
  • Name: Ken Burns
  • Gender: M
  • Age: 50
  • Race: Caucasian
  • Cancer: Head and neck
  • Type: Squamous cell carcinoma
  • Cancer site: Oropharynx
  • Diagnosis: Base of tongue carcinoma
  • Cancer stage: IVB
  • Treatment: Concurrent chemoradiotherapy
Patient introduction

Ken is a 50 year old Caucasian man who was shaving in the bathroom one day when he noticed a swollen lump on his neck. Not thinking much of it, he decided to ignore the enlarged mass and wait for it to subside. Two weeks later, the lump was still there.

Clinical assessment

After a visit to the doctor’s office, Ken’s primary care physician asked him a series of questions regarding his medical history and daily habits. A comprehensive patient history was taken, and questions inquiring into his daily activities and recreational habits were also asked to assess possible risk factors, including recreational drug use, sexual activity including number of recent sexual partners, smoking history and alcohol consumption.

With help from his doctor, Ken estimated that his smoking activity over the years amounted to ten pack-years, and indicated that he had quit a few years ago. Ken also admitted to having multiple sexual partners over the years, though he wasn’t sure how that would help in determining his diagnosis. He had no family history of cancer, no history of recreational drug use and was not a fan of alcohol, drinking only during holidays and on special occasions.

Taking into account these findings, Ken’s primary care doctor ordered several tests and diagnostic images to be performed. A small sample of tissue was taken to check for signs of cancer and human papillomavirus (HPV). Computed tomography (CT) scans were also taken for a better picture of activity within the head and neck region.

Biopsy results showed a histology of squamous cell carcinoma from the tumor site with poorly differentiated cancer cells, and the pathology report on Ken’s HPV status came back as positive. Based on information about Ken’s updated patient history and risk factors, as well as results from diagnostic tests and imaging, ultimately a diagnosis was made for base of tongue carcinoma. The physician carefully assessed all findings and Ken’s cancer was staged as IVB with TNM of 1, 3, 0. This clinical stage at presentation is consistent with studies which have shown that HPV-positive oropharyngeal squamous cell carcinoma tumors more likely present with early T stage (i.e., T1-T2), advanced N stage (i.e., usually cystic and multi-level), and have distinct histological features showing moderate or poor tumor differentiation.1

Pack-year:

    • Pack-year is a measure of the amount of cigarettes smoked over a period of time, calculated by multiplying the number of cigarette packs smoked per day by the number of years that person has smoked
    • For example, 1 pack year is equal to smoking 1 pack, i.e., 20 cigarettes, per day for 1 year, or 2 packs, i.e., 40 cigarettes, per day for half a year, and so on

TNM:

    • T stands for “tumor” and describes the tumor size and any cancer spread into nearby tissue
    • N stands for “node” and describes cancer spread to nearby lymph nodes
    • M stands for “metastasis” and describes cancer spread to other parts of the body
Head and neck cancer

Head and neck cancer is a collective group of cancers that starts in the mouth, nose, throat, larynx, sinus, or salivary gland. These cancers account for approximately 4% of all cancers in the United States2 and about 95% of these are squamous cell carcinomas. Cancers of the head and neck can be categorized by the site in which the cancer begins: oral cavity, oropharynx, nasopharynx, hypopharynx, glottis (larynx), or sinus. In the case of Ken, the tumor is located at the base of the tongue, which is part of the oropharynx.

Head and neck cancers are more than twice as common among men as they are among women3 and diagnosed more often among people over 50 years of age. Tobacco use, heavy alcohol use, and HPV infection increase the risk of head and neck cancers.

Base of tongue carcinoma

Base of tongue carcinoma is a type of head and neck cancer that develops in the back third of the tongue. Most base of tongue cancers are squamous cell carcinomas which form in the thin and flat cells that line the larynx, thyroid, throat, nose, and mouth. The area of the base of tongue is part of the oropharynx, which includes the tonsils, walls of the throat, and soft palate4.

The image of the oropharynx is taken from the BodyMap VR application.

Ken, being male, middle-aged, Caucasian, HPV-positive, having a moderately high level of sexual activity with multiple partners, with histology of poorly-differentiated squamous cell carcinoma, fits the profile of a patient having characteristics consistent with HPV-positive oropharyngeal cancer:

  • Male: male-to-female ratio is 2:1 for cancers of the oral cavity and oropharynx5 and at least 3:1 for HPV-associated invasive squamous cell carcinoma of the oropharynx and oral cavity6
  • Age: HPV-positive oropharyngeal squamous cell carcinoma patients have a median age of diagnosis at 54 years7
  • Caucasian: white males have the highest overall incidence of oral cancer among all races and ethnicity groups8, and HPV-associated oropharyngeal squamous cell carcinoma in particular primarily affects whites and men9
  • HPV-positive: HPV is a major etiologic factor associated with oropharyngeal cancer, with HPV being detected in up to 80% of oropharyngeal cancers10
  • Multiple sexual partners: sexual activity involving early first sexual relations, multiple partners, or oral sex, is characteristic of HPV-positive patients who have head and neck cancer located at the base of the tongue11; also, sexual behaviors are typically associated with HPV-positive head and neck squamous cell carcinomas but not with HPV-negative head and neck squamous cell carcinomas, which are mostly caused by tobacco and alcohol use12
  • Histology: HPV-related oropharyngeal squamous cell carcinomas tend to be poorly differentiated13
Treatment planning

After an extensive discussion on possible treatment options, Ken’s healthcare team decided to proceed with an oncologic treatment plan involving concurrent chemoradiotherapy treatment without induction chemotherapy or surgery.

Concurrent chemoradiotherapy:

Concurrent delivery of chemotherapy and radiotherapy, where ‘concurrently’ means that the two forms of treatment may overlap or occur on the same day(s); for example, at times, radiotherapy and chemotherapy are delivered on the same day, and on other days, only radiotherapy is delivered

Radiotherapy

Prior to the actual start date of initiating radiation treatment, the radiation oncologist arranged for Ken to go through a simulation process that involved placing Ken on a simulation machine, measuring his body and marking parts of immobilization devices to make sure that during actual radiotherapy, radiation beams would be delivered safely and precisely to the intended locations11. Making the appropriate preparations and mapping out exact locations of where the treatment beams would be delivered is an important step prior to proceeding with actual radiotherapy treatment.

Immobilization device:

Immobilization devices help the patient to remain in the same position for each radiation therapy session, and can include molds, casts, headrests, masks, and other devices

During simulation, a CT scan was used to capture images of Ken’s tumor and normal tissue from various angles, and specifically at areas to be treated with radiation. The radiation therapist carefully guided Ken through the simulation process to create a treatment position that was accurate, reproducible, and specific to Ken’s requirements by using a combination of immobilization devices including masks, leg molds, headrests, sponges, and pillows.12

This CT simulation process which typically takes place approximately one week prior to the first actual radiotherapy session is important for Ken’s healthcare team to be able to properly perform accurate treatment planning and calculate the exact dose of protons to be precisely delivered to the target tumor.13

The Cancer Library VR in-app view below shows a snapshot of Ken’s base of tongue cancer in the head and neck region with tumor segmentation highlighted. Cancer Library VR app users can select tumor segmentations, which have been manually annotated by actual radiologists, that they wish to visualize alongside other anatomical structures.

The image above is taken from the Cancer Library VR, and contains image and clinical data obtained from The Cancer Imaging Archive (TCIA), HNSCC Collection (TCIA subject ID: HNSCC-01-0054), with anonymized patient data and de-identified radiotherapy simulation scan showing physician- and dosimetrist-contoured target and avoidance volumes.

Chemotherapy

For the chemotherapy portion of the concurrent chemoradiotherapy treatment, Ken’s physician considered various chemotherapy agents and prescribed carboplatin, an agent best indicated for Ken and commonly used concurrently with radiotherapy.

Treatment summary

Ultimately, Ken’s treatment plan involved weekly administration of the chemotherapy agent carboplatin at a dose of AUC 2.0, given concurrently with a radiation dose of 70 Gy in 35 fractions to the tumor, taking place over a treatment period of 30 days.

Follow-up

By following his healthcare team’s carefully crafted concurrent chemotherapy treatment plan, Ken successfully achieved complete response. At the most recent follow-up appointment between Ken and his primary care physician, taking place just over 7 years after completing radiotherapy treatment, Ken was assessed to be alive and healthy without cancer recurrence, with a disease-free interval of over 88 months.

Ken’s healthcare team, and particularly the team in charge of Ken’s radiation treatment portion, were not all that surprised to learn about this happy outcome, as studies have shown that HPV-related oropharyngeal squamous cell carcinoma is extremely sensitive to radiation exposure and those indicated for treatment tend to be complete responders and long-term survivors.14

This positive outcome is also consistent with studies showing that, in general, treatment outcome is much better and more curable when the cancer in question is HPV-related rather than tobacco- and alcohol-related15.

In fact, throughout the visits to the doctor’s office and discussions on treatment plans, Ken often had concerns that he would not beat this cancer, or even if the cancer were treated that it would return at a later date. He found himself increasingly regretful about certain liberties he took in his personal life, such as thoughts that he should have toned down his sex life involving multiple partners.

However, Ken’s physician offered reassurance through several research studies demonstrating that being HPV-positive in his case was not actually worse than being HPV-negative. In actuality, patients with HPV-positive base of tongue cancer had a significantly better overall and disease-free survival compared to those with HPV-negative tumors16. HPV-positive oropharyngeal cancer patients have 28-80% reductions in risk of death compared to HPV-negative patients, and are relatively much more likely to have improved outcomes17.

Ken now lives with his two dogs and has, since finishing treatment, largely abstained from some of his previous hobbies and used the extra time to pursue new interests such as swimming and cycling. His advice to anyone facing a similar situation is to properly research and find an experienced physician and specialist team including radiation oncologists and radiation therapists who will be able to form an effective treatment plan and deliver the best possible care.

Fact:

    • Patients with HPV-positive oropharyngeal squamous cell carcinoma tend to have a more favorable prognosis and quality of life than those with HPV-negative oropharyngeal squamous cell carcinoma.18
References
  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299160/
  2. https://www.cancer.net/cancer-types/head-and-neck-cancer/statistics
  3. https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/about/key-statistics.html
  4. https://utswmed.org/conditions-treatments/base-tongue-cancer/
  5. https://emedicine.medscape.com/article/1289474-overview
  6. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.23745
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532587/
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385715/
  9. https://www.slideshare.net/priyankshah965/latest-presentation-of-hpv-in-head-and-neck
  10. https://www.nature.com/articles/modpathol2016152#Tab1
  11. https://radiationoncology.uw.edu/radiation-treatment/your-first-visit/
  12. https://www.sccaprotontherapy.com/getting-treatment/simulation-and-planning
  13. https://radiationoncology.emory.edu/patients/treatments/ct_simulation.html
  14. https://www.hindawi.com/journals/jo/2019/9173729/
  15. https://www.medicaldosimetry.org/default/assets/File/denver2018/Zurek_Head_and_Neck_Cancer_in_The_Emerging_Era.pdf
  16. https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.25625
  17. https://pubmed.ncbi.nlm.nih.gov/22782220/
  18. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/1847508

Special acknowledgement to the researchers and institutions that provided the HNSCC collection datasets on TCIA:

Data Citation

Grossberg  A, Mohamed A, Elhalawani H, Bennett W, Smith K, Nolan T, Chamchod S, Kantor M, Browne T, Hutcheson K, Gunn G, Garden A, Frank S, Rosenthal D, Freymann J, Fuller C.(2017).  Data from Head and Neck Cancer CT Atlas. The Cancer Imaging Archive.  DOI: 10.7937/K9/TCIA.2017.umz8dv6s

Publication Citation

Grossberg  A, Mohamed A, Elhalawani H, Bennett W, Smith K, Nolan T,  Williams B, Chamchod S, Heukelom J, Kantor M, Browne T, Hutcheson K, Gunn G, Garden A, Morrison W, Frank S, Rosenthal D, Freymann J, Fuller C. (2018) Imaging and Clinical Data Archive for Head and Neck Squamous Cell Carcinoma Patients Treated with Radiotherapy. Scientific Data 5:180173 (2018) DOI: 10.1038/sdata.2018.173

TCIA Citation

Clark K, Vendt B, Smith K, Freymann J, Kirby J, Koppel P, Moore S, Phillips S, Maffitt D, Pringle M, Tarbox L, Prior F. (2013) The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository, Journal of Digital Imaging, 26:6 pp 1045-1057. DOI:  10.1007/s10278-013-9622-7

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