Mature results of a prospective study of deintensified chemoradiotherapy for low-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma.

BACKGROUND: The purpose of the current study was to determine quality of life and tumor control from a prospective phase 2 clinical trial evaluating deintensified chemoradiotherapy for favorable risk, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. METHODS: Patients with T0-T3, N0-N2c, M0, p16-positive disease and a minimal smoking history were treated with 60 grays of intensity-modulated radiotherapy with concurrent weekly intravenous cisplatin (30 mg/m2 ). The primary study endpoint was the pathologic complete response rate based on biopsy of the primary site and dissection of pretreatment positive lymph node regions. The pathologic complete response rate as previously reported was 86%. Herein, the authors report secondary endpoint measures of local control, regional control, cause-specific survival, distant metastasis-free survival, and overall survival, and patient-reported outcomes (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [EORTC QLQ-C30] and the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events [PRO-CTCAE]). RESULTS: A total of 44 patients enrolled with a median follow-up of 36 months (88% with ≥2 years). The 3-year local control, regional control, cause-specific survival, distant metastasis-free survival, and overall survival rates were 100%, 100%, 100%, 100%, and 95%, respectively. The mean before and 3-year after EORTC QOL scores were: global: 80 of 78; swallowing: 11 of 11; dry mouth: 16 of 41; and sticky saliva: 6 of 29. The mean before and 3-year after PRO-CTCAE scores were: swallowing: 0.4 of 0.7; and dry mouth: 0.4 of 1.4. Approximately 39% of patients required a feeding tube (median duration, 15 weeks; none were permanent). There were no ≥grade 3 late adverse events reported. CONCLUSIONS: For patients with favorable-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma, a substantially decreased intensity of therapy with 60 grays of intensity-modulated radiotherapy and weekly low-dose cisplatin produced better preservation of quality of life compared with standard therapies while maintaining excellent 3-year tumor control and survival. Cancer 2018;124:2347-54. © 2018 American Cancer Society.

Follicular thyroid carcinoma metastasis to the facial skeleton: a systematic review.

BACKGROUND: Follicular thyroid carcinoma (FTC) metastasis to the facial skeleton is exceedingly rare. A case of FTC metastasizing to the mandible is presented and a systematic review of the literature describing thyroid metastasis to the facial skeleton is performed. CASE PRESENTATION: A 73-year-old female presented with metastatic FTC to the mandible and underwent total thyroidectomy, segmental mandibulectomy, bone impacted fibular free flap reconstruction, and adjuvant radioactive iodine treatment. The PubMed database was searched for literature describing thyroid cancer with facial skeleton metastasis using the key words "thyroid," "cancer," "carcinoma," "metastasis," and "malignancy" with "oral cavity," "maxilla," "mandible," "sinus," "paranasal," and "orbit." Reports that only involved the soft tissues were excluded. Systematic review revealed 59 cases of well-differentiated thyroid cancer with facial skeleton metastasis: 35 mandibular metastases (21 = FTC), 6 maxilla metastases (2 = FTC), 9 orbital metastases (4 = FTC), and 11 paranasal sinus metastases (7 = FTC). Treatment included surgery, RAI, external beam radiotherapy (XRT), or a combination of these modalities. The one, two, and five-year survival rates were 100%, 79%, and 16%, respectively. CONCLUSION: Facial skeleton metastasis of FTC is a rare clinical challenge. Optimal treatment appears to include total thyroidectomy and resection of involved structures with or without adjuvant treatment.

Retromolar trigone squamous cell carcinoma treated with radiotherapy alone or combined with surgery: a 10-year update.

PURPOSE/OBJECTIVES: Treatment outcomes were analyzed for patients who received radiotherapy for squamous cell carcinoma of the retromolar trigone at a single institution. MATERIALS/METHODS: We reviewed the medical records of 110 patients treated with radiotherapy alone (n=36) or radiotherapy combined with surgical resection of the primary tumor (n=74) between June 1966 and October 2013. The median follow-up was 4.5years for all patients and 11.8years for living patients (range, 1.3-23.5years). RESULTS: The 5-year local-regional control rates after definitive radiotherapy versus surgery and radiotherapy for stages I-III were 52% and 89% and for stage IV they were 46% and 58%, respectively. The 5-year cause-specific survival rates after definitive radiotherapy compared with surgery and radiotherapy for stages I-III were 57% and 82% and for stage IV they were 45% and 43%, respectively. Multivariate analyses revealed that the likelihood of cure was better with surgery and radiotherapy compared with radiotherapy alone (p=0.041). CONCLUSION: Patients treated with surgery and radiotherapy had a better chance of cure than those treated with radiotherapy alone. Complications of treatment were common in both groups but more common in patients who underwent surgery.

Challenging the Requirement to Treat the Contralateral Neck in Cases With >4 mm Tumor Thickness in Patients Receiving Postoperative Radiation Therapy for Squamous Cell Carcinoma of the Oral Tongue or Floor of Mouth.

HYPOTHESIS: While treating patients with postoperative radiotherapy (RT) for squamous cell carcinoma of the oral tongue or floor of mouth, we hypothesized a low risk of tumor recurrence in the contralateral neck in the absence of contralateral neck RT when the primary tumor is >1 cm from the midline regardless of tumor thickness (TT) or depth of invasion (DOI)>4 mm. OBJECTIVE: The policy at our institution for many years has been to limit postoperative RT to the ipsilateral side when the primary tumor does not cross the midline, regardless of TT or DOI. We report the rate of isolated contralateral neck failure in this group. MATERIALS AND METHODS: We retrospectively reviewed all patients treated with postoperative RT at our institution between 1998 and 2014 for pathologic stage T1-T4 N1-N2b squamous cell carcinoma of the oral tongue or floor of mouth that did not cross the midline and thus were treated with RT limited to the primary site +/- ipsilateral neck. RESULTS: Our study population included 32 patients: 75% with close (<5 mm) or positive margins and 38% with perineural invasion. No patients had a tumor that crossed the midline. TT was ≥4 mm in 75% of patients. DOI was >5 mm in 68% of patients. There were no isolated contralateral neck recurrences with a median follow-up of 5 years. CONCLUSION: While delivering postoperative RT for oral tongue or floor of mouth cancer with pathologic neck stage N0-2b, the risk of not irradiating the contralateral neck is very low when the primary tumor does not cross the midline, regardless of other factors at the primary site, such as TT and DOI.

Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: To report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: Major inclusion criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) being p16 positive, and (3) reporting minimal or remote smoking history. Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m2 once per week. Patients with T0-T2 N0-1 (AJCC 7th edition) did not receive chemotherapy. All patients had a 10- to 12-week post-treatment positron emission tomography/computed tomography to assess for neck dissection. The primary end point was 2-year progression-free survival. Secondary end points included 2-year local-regional control, distant metastasis-free survival and overall survival, and patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events). RESULTS: One hundred fourteen patients were enrolled (median follow-up of 31.8 months), with 81% having a minimum follow-up of 2 years. Eighty percent of patients had 10 or fewer tobacco pack-years. Two-year local-regional control, distant metastasis-free survival, progression-free survival, and overall survival were as follows: 95%, 91%, 86%, and 95%, respectively. Mean pre- and 2-year post-treatment European Organisation for Research and Treatment of Cancer quality of life scores were as follows: global, 79/84 (lower worse); swallowing, 8/9 (higher worse); and dry mouth, 14/45 (higher worse). Mean pre- and 2-year post-treatment patient-reported outcomes version of the Common Terminology Criteria for Adverse Events scores (0 to 4 scale, higher worse) were as follows: swallowing, 0.5/0.7, and dry mouth, 0.4/1.3. Thirty-four percent of patients required a feeding tube (median, 10.5 weeks; none permanent). There were no grade 3 or higher late adverse events. CONCLUSION: Clinical outcomes with a de-intensified chemoradiotherapy regimen of 60 Gy intensity-modulated radiotherapy with concurrent low-dose cisplatin are favorable in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. Neither neoadjuvant chemotherapy nor routine surgery is needed to obtain favorable results with de-escalation.

Quality of Life for Patients With Favorable-Risk HPV-Associated Oropharyngeal Cancer After De-intensified Chemoradiotherapy.

PURPOSE: Oropharynx cancers associated with human papillomavirus (HPV) have a favorable prognosis, but current treatment approaches carry significant long-term morbidity. Strategies to de-intensify treatment in this population are under investigation, but the impact of these approaches on quality of life (QOL) is not well understood. We present patient-reported outcomes from 2 prospective studies examining de-intensified chemoradiotherapy. METHODS AND MATERIALS: This study included patients enrolled in 2 prospective phase 2 trials of de-intensified chemoradiotherapy in patients with HPV-associated oropharynx cancer who had at least 1 year of follow-up. Treatment included concurrent radiation therapy (60 Gy) and chemotherapy (weekly cisplatin, 30 mg/m2). Patients reported QOL and symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module-35, and the Eating Assessment Tool-10 instruments before treatment and at regular intervals thereafter. Changes in QOL and individual symptoms were examined over time, and multivariate analysis was used to identify clinical factors associated with recovery to baseline symptom levels. RESULTS: Of the 154 patients enrolled, 126 patients had at least 1 year of follow-up and were included in this study (median follow-up, 25 months). Global QOL, functional indices, and most individual symptoms returned to baseline 3 to 6 months after treatment. Swallowing (Eating Assessment Tool-10 score) returned to baseline function by 2 years, but dry mouth, sticky saliva, and taste/senses did not return to baseline levels. However, from 1 to 2 years, continued improvement occurred in dry mouth score (55 vs 48), sticky saliva score (35 vs 27), and senses score (24 vs 20). On multivariate analysis, unilateral radiation therapy was associated with returning to baseline level of swallowing and sticky saliva. CONCLUSIONS: The use of de-intensified chemoradiotherapy in HPV-associated oropharynx cancer led to favorable patient-reported outcomes, with early recovery of QOL and continued improvement of xerostomia and dysphagia beyond 1-year posttreatment.

Long-term Outcomes Following Radiotherapy for Adolescent Patients With Nonmetastatic WHO Type III Nasopharyngeal Carcinoma.

OBJECTIVES: To report long-term results of primary radiotherapy for nasopharyngeal cancer (NPC) presenting in the adolescent group. METHODS: Ten adolescent patients with World Health Organization (WHO) type III NPC were treated with primary radiotherapy at our institution between 1969 and 2007. Median age was 16.5 years (range, 11 to 21). Median radiotherapy dose to the primary target volume was 67.5 Gy (range, 60 to 74.8). The bilateral neck received 51.1 Gy (range, 50 to 60 Gy). Five patients were treated with once-daily radiotherapy and 5 received twice-daily radiotherapy. Three patients received neoadjuvant cisplatin and 5FU, and 1 patient received adjuvant maintenance cisplatin and 5FU. RESULTS: Median follow-up time was 9.5 years (range, 1.94 to 34.74). Fifteen-year overall survival, cause-specific survival, and progression-free survival rates were all 70%. Fifteen-year local and regional control rates were 100% and 90%. One patient recurred regionally and distantly simultaneously, and 2 patients developed distant metastases alone. All 3 died of their disease within 3 years. One patient died from multiple radiation-induced secondary meningiomas 34 years after radiotherapy. Five patients developed hypothyroidism, 3 developed sensorineural hearing loss, and 4 developed dental complications. The overall rates of CTCAE grade 3, 4, and 5 toxicity were 40%, 10%, and 10%, respectively. Despite high-radiation doses to the skull base, none of the patients in this study developed grade 3+ cognitive or vision toxicity. CONCLUSIONS: Radiotherapy achieves excellent local control in adolescent patients with unresectable WHO type III NPC. Our data support current protocols to systematically tailor treatment volumes and deescalate radiation doses to reduce treatment toxicity.

Matching IMRT fields with static photon field in the treatment of head-and-neck cancer.

Radiation treatment with intensity-modulated radiation therapy (IMRT) for head-and-neck cancer usually involves treating the superior aspects of the target volume with intensity-modulated (IM) fields, and the inferior portion of the target volume (the low neck nodes) with a static anterior-posterior field (commonly known as the low anterior neck, or LAN field). A match line between the IM and the LAN fields is created with possibly large dose inhomogeneities, which are clinically undesirable. We propose a practical method to properly match these fields with minimal dependence on patient setup errors. The method requires mono-isocentric setup of the IM and LAN fields with half-beam blocks as defined by the asymmetric jaws. The inferior jaws of the IM fields, which extend approximately 1 cm inferiorly past the isocenter, are changed manually before patient treatment, so that they match the superior jaw of the LAN field at the isocenter. The matching of these fields therefore does not depend on the particular treatment plan of IMRT and depends only on the matching of the asymmetric jaws. Measurements in solid water phantom were performed to verify the field-matching technique. Dose inhomogeneities of less than 5% were obtained in the match-line region. Feathering of the match line is done twice during the course of a treatment by changing the matching jaw positions superiorly at 3-mm increments each time, which further reduces the dose inhomogeneity. Compared to the method of including the lower neck nodes in the IMRT fields, the field-matching technique increases the delivery efficiency and significantly reduces the total treatment time.

An immobilization system for claustrophobic patients in head-and-neck intensity-modulated radiation therapy.

PURPOSE: To evaluate the effectiveness of an immobilization treatment system used for claustrophobic patients in head-and-neck intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Instead of the thermoplastic facemask, the Vac Fix (S & S Par Scientific, Odense, Denmark) mold is used for immobilization of claustrophobic patients at the University of Florida in head-and-neck IMRT. The immobilization procedure combines the use of commercial stereotactic infrared (IR) ExacTrac camera system (BrainLAB, Inc., Westchester, IL) for patient setup and monitoring. The Vac Fix mold is placed on the headrest and folded up as needed to provide support before the mold is hardened. For the camera system, a frame referred to as a "tattoo-free immobilization accessory" is fabricated, on which the IR markers can be placed. A patient-specific dental impression is made with the bite tray. The movement of the markers, connected through the dental impression of the patient, accurately represents the overall patient motion. Patient movement is continuously monitored and repositioning is performed whenever patient movement exceeds the predefined tolerance limit. Monitored patient movements are recorded at a certain frequency. Recorded data are analyzed and compared with those of patients immobilized with the thermoplastic facemask plus the camera system that is the standard immobilization system in our clinic. RESULTS: For three patients treated with the Vac Fix mold plus the camera system, on average, the histogram-based uncertainties, U(95)(5), U(95)(20), and mean displacement, R(mean) (mm) were 1.03, 1.08, and 0.60, respectively. These values are close to those obtained with the mask plus the camera system. The Vac Fix mold plus the camera system often requires more beam interruptions because of repositioning than the mask plus the camera system (on average, the Vac Fix mold plus the camera system required repositioning 7.7 times and the mask plus the camera system required repositioning 1.8 times during 20 treatments). CONCLUSION: The Vac Fix mold immobilization procedure plus the camera monitoring system has been set up for patients who are claustrophobic or cannot tolerate a mask during head-and-neck IMRT. Although this system causes more frequent beam delivery interruptions, it is as effective as the mask plus the camera system in immobilizing patients within the tolerance limit.

Ewing tumors of the head and neck.

PURPOSE: Retrospective review describing the 40-year University of Florida experience treating Ewing tumors of the head-and-neck region with a summary of the pertinent literature. PATIENTS AND METHODS: Nine patients were diagnosed and treated for Ewing sarcoma of the head and neck at our institution between 1965 and 2007. Primary sites included: mandible (3 patients), calvarium (2 patients), paranasal sinus (2 patients), oral cavity (1 patient), and the extraosseous soft tissue of the neck (1 patient). The median age at diagnosis was 13.0 years (range, 6.3-20.1 years). The median observed follow-up was 10.2 years (range, 1.5-37 years). RESULTS: All patients received multiagent chemotherapy and radiation therapy to a median dose of 55.8 Gy (range, 36-67.2 Gy). Three patients also underwent wide local excision. The actuarial 10-year overall survival, cause-specific survival, event-free survival, and local control probabilities were 66%, 66%, 56%, and 89%, respectively. Late complications included poor dentition, mild xerophthalmia, cataract, and mandibular hypoplasia. A literature search revealed 8 previous series with Ewing tumors of the head and neck analyzed as subsets of larger studies. CONCLUSIONS: In the context of limited data on head and neck Ewing tumors, combined modality therapy provides excellent local control with reasonable acute and late toxicity. Large tumors were associated with poor disease control.

Do pre-irradiation dental extractions reduce the risk of osteoradionecrosis of the mandible?

BACKGROUND: This study was done to determine if pre-radiotherapy (pre-RT) dental extractions reduce the risk of osteoradionecrosis (ORN). METHODS: Between 1987 and 2004, 413 patients with oropharyngeal carcinomas were treated with definitive RT at the University of Florida. Dentate patients underwent pretreatment dental evaluation. Teeth in the RT field were usually extracted if thought to have poor long-term prognosis from dental disease. The endpoint was > or = grade 2 ORN using a modified staging system. Patients were excluded for local recurrence, additional RT above the clavicles, or head and neck surgery besides neck dissection. RESULTS: ORN rates were as follows: edentulous, <1%; teeth in-field with pre-RT extractions, 15%; and teeth in-field without pre-RT extractions, 9%. Patients with poor in-field teeth and pre-RT extractions had a higher 5-year incidence of ORN than those who did not have pre-RT extractions (16% vs 6%, p = .48). Likewise, for those with in-field teeth in good condition and pre-RT extractions, the 5-year ORN incidence was higher than for those who did not undergo extractions (15% vs 2%, p = .42). Multivariate analysis revealed increased ORN risk with doses of >70 Gy, once-daily fractionation, or brachytherapy. CONCLUSION: Pre-RT extractions do not appear to reduce the risk of ORN.