Search

Purpose: Patients with p16 positive tonsillar cancer (p16 + TC) have an excellent prognosis and long-life expectancy. Deintensification of therapy is a prevalent topic of discussion. Proton radiotherapy is one way to reduce radiation exposure and thus reduce acute and late toxicity. The aim is to evaluate treatment outcomes and toxicity of postoperative treatment with intensity-modulated proton therapy (IMPT)., Methods: Between September 2013 and November 2021, 47 patients with p16 + TC were treated postoperatively with IMPT. Median age was 54.9 (38.2-74.9) years, 31 were males and 16 were females. All patients had squamous cell carcinoma and underwent surgery as a primary treatment. Median dose of radiotherapy was 66 GyE in 33 fractions. Bilateral neck irradiation was used in 39 patients and unilateral in 8. Concomitant chemotherapy was applied in 24 patients., Results: Median follow-up time was 4.2 (0.15-9.64) years. Five-year overall survival, relapse free survival and local control were 95.7%, 97.8% and 100%. The most common acute toxicities were dermatitis and mucositis, with grade 2 + in 61.7% and 70.2% of patients. No acute percutaneous gastrostomy insertion was necessary and intravenous rehydration was used in 12.8% of patients. The most common late toxicity was grade 1 xerostomia in 70.2% of patients and grade 2 in 10.6% of patients. Subcutaneous fibrosis of grades 2 and 3 occurred in 17.0% and 2.1% of patients, respectively. One patient developed late severe dysphagia and became PEG-dependent., Conclusion: IMPT for the postoperative treatment of p16 + TC is feasible with excellent efficiency and acceptable acute and late toxicity., (© 2024. The Author(s).)

Treatment of squamous cell carcinoma of the tonsil involves primary radiation therapy (RT) or surgical resection. Historically, if RT was the primary or adjuvant treatment modality, most of the bilateral retropharyngeal lymph nodes (RPLNs) were treated electively with a therapeutic dose for subclinical disease, regardless of whether radiographically pathologic lymph nodes were seen on initial diagnostic imaging. De-escalation strategies include the incorporation of transoral surgery with the goal to either eliminate or reduce the dose of adjuvant RT or chemotherapy. Transoral surgery does not include elective removal of the RPLNs, and no guideline or outcome paper recommends adjuvant RT specifically to electively treat RPLNs. In this Topic Discussion, we discuss pertinent literature and suggest management decisions. The management decisions discussed in this Topic Discussion pertain to only tonsillar primaries and not those of the soft palate or base of the tongue., Competing Interests: Disclosures None., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Abstract: Radiation therapy is often accompanied by skin toxicity in the irradiated area and radiation-induced DNA damage to skin tissue cells in the surrounding pigmented area. This case report describes a patient with radiation-induced skin injury who received wound treatment and psychological intervention with satisfactory results. A 60-year-old woman was admitted to the authors' hospital on January 18, 2021, with radiation-induced skin injury caused by carbon ion radiotherapy for tonsillar carcinoma. The patient underwent wound repair combined with psychological intervention (30 minutes per dressing change). Over a period of 1 month, the wound area was reduced from 11 × 12 cm2 to 1 × 1 cm2, and wound symptoms (exudate, blood odor, wound infection, wound edge dehydration and curling, periwound skin peeling, dryness, and hyperkeratosis) improved. The patient's anxiety factor scores decreased from 18 to 1, and her depression factor scores decreased from 16 to 3. When the patient was discharged from the hospital after 1 month of treatment, she had a satisfactory self-image and normal social activities., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.

Importance: Ipsilateral neck radiotherapy (RT) is controversial in some patients with tonsil cancer due to concern for nodal failure within the contralateral nonirradiated neck (hereinafter referred to as contralateral neck failure [CNF])., Objective: To determine the rate of CNF following ipsilateral neck RT in patients with tonsil cancer., Data Sources: Databases including PubMed, Embase, Web of Science, and Cochrane Library were queried for peer-reviewed, English language articles published between January 1, 1980, and December 31, 2021., Study Selection: Studies reporting rates of CNF from at least 20 patients treated with ipsilateral neck RT. Studies were excluded if they lacked full text, reported results from databases or systematic reviews, or did not provide RT details., Data Extraction and Synthesis: Data were extracted following the PRISMA reporting guideline. Study quality was assessed using criteria from a methodological index for nonrandomized studies. Pooled outcomes were estimated using random-effects models., Main Outcomes and Measures: Primary outcome was the pooled rate of CNF following ipsilateral neck RT. Secondary outcomes were the pooled rates of CNF by tumor and nodal staging categories from the 7th edition of the AJCC Cancer Staging Manual and rates of toxic effects., Results: A total of 17 studies (16 retrospective and 1 prospective) including 1487 unique patients were identified. The pooled risk of CNF was 1.9% (95% CI, 1.2%-2.6%). The rate of CNF by tumor (T) category was as follows: 1.3% (95% CI, 0.3%-2.3%) for T1; 3.0% (95% CI, 1.6%-4.4%) for T2; 11.3% (95% CI, 3.3%-19.2%) for T3; and 16.0% (95% CI, -7.8% to 39.8%) for T4. Patients with T3 to T4 tumors had a significantly higher rate of CNF than those with T1 to T2 tumors (11.5% [95% CI, 3.9%-19.1%] vs 1.8% [95% CI, 1.0%-2.6%]; P < .001). The rate of CNF by nodal (N) category was 1.2% (95% CI, 0.1%-2.2%) for N0; 4.8% (95% CI, 2.4%-7.2%) for N1; 3.1% (95% CI, 0.4%-5.8%) for N2a; 3.1% (95% CI, 1.2%-4.9%) for N2b; and 0 (95% CI, not applicable) for N3. Rates of CNF were similar for patients with N2b to N3 and N0 to N2a disease (3.0% [95% CI, 1.2%-4.7%] vs 1.7% [95% CI, 0.6%-2.8%], respectively; P = .07). Compared with bilateral RT, ipsilateral RT was associated with increased risk of CNF (log odds ratio, 1.29 [95% CI, 0.09-2.48]; P = .04). The crude rates of xerostomia of grade 3 or greater and feeding tube use were 0.9% (95% CI, -0.2% to 1.9%) and 13.3% (95% CI, 8.3%-18.3%), respectively., Conclusions and Relevance: In this systematic review and meta-analysis, ipsilateral neck RT was associated with a low rate of CNF in patients with small, lateralized tonsil cancers. Bilateral neck RT was associated with lower risk of CNF compared with ipsilateral neck RT. Patients with tumors of a higher T category were at increased risk for CNF following ipsilateral neck RT, and advanced nodal stage was not associated with CNF. Rates of toxic effects appeared favorable in patients treated with ipsilateral neck RT.

Purpose: The aim of this TROG 12.01 substudy was to report longitudinal variations in patient- (PRO) and clinician-reported outcomes based on receipt of unilateral (URT) or bilateral radiation therapy (BRT)., Methods and Materials: Patients with lateralized T1-2 N1-2b human papillomavirus-associated tonsillar carcinoma (AJCC7) enrolled on TROG 12.01 were eligible. The primary endpoint was patient-reported radiation symptom severity score (MDASI-RSS) at 2 years, a composite of 9 MDASI-Head and Neck (HN) symptom items. Secondary endpoints included patient-reported symptom burden and interference (MDASI-HN), quality of life (FACT-HN), emotional distress (HADS), return to work (RTW), clinician-reported performance status scale (PSS-HN), and late adverse events (CTCAE). Mean MDASI-RSS, symptom severity (MDASI-SS), symptom interference (MDASI-SI) and selected single items were compared 1 week, 3 months, and 2 years post-RT., Results: Seventy-four patients were eligible for analysis (26 URT, 48 BRT). Median follow-up was 3.7 years (1.8-5.2 years). Sociodemographic, staging, and treatment variables were mostly balanced, with larger primaries observed in the BRT group. Four regional failures were reported (3 URT, 1 BRT), including one isolated contralateral regional failure in the URT cohort. Mean MDASI-RSS scores did not differ at 2 years (URT vs BRT, 1.1 vs 1.3; difference 0.1 [95% CI: -0.7 to 0.9], P = .75) or at any other time points for the MDASI-RSS, MDASI-SS, and MDASI-SI scores, except for worse MDASI-SI 1 week after treatment in the BRT group (4.7 vs 5.6). Fatigue (6.6 vs 5.4) at 1 week and dry mouth (3.5 vs 2.0) at 2 years were also worse in the BRT group. FACT-HN, HADS, RTW, PSS-HN, and CTCAE results were similar across the follow-up period., Conclusions: In this favorable-risk cohort, treatment laterality resulted in fewer differences than anticipated in patient-reported or clinician-reported outcomes. Two years after treatment patients treated with BRT reported significantly worse dry mouth. Longer follow-up is needed to determine the impact of treatment laterality on late effects., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Human papillomavirus (HPV)-positive tonsil cancer has a better prognosis than HPV-negative tonsil cancer. Deintensification strategies to reduce or avoid radiotherapy (RT) for patients with HPV-associated tonsil cancer have been suggested. This study investigated the treatment outcomes of patients with HPV-associated tonsil cancer and suggested RT deintensification strategies., Methods: A cohort of 374 patients with HPV-associated tonsil cancer treated with primary surgery or RT between 2008 and 2020 was retrospectively evaluated. Survival and locoregional control rates after primary surgery or RT were analyzed, and propensity score matching was performed to adjust for clinical factors. Pearson's chi-square or Fisher's exact test was used to compare categorical variables, and Student's t-test was used to compare continuous variables. The Kaplan-Meier method and log-rank test were used to assess overall survival, progression-free survival, and locoregional failure (LRF)., Results: No significant differences in survival or LRF were observed between the primary surgery and RT groups. Subgroup analysis was conducted for patients who underwent primary surgery. Advanced pathological N stage, negative contralateral nodes at diagnosis, abutting or positive surgical margins, and no adjuvant RT were independent risk factors for LRF. Advanced pathological T stage was an independent risk factor for LRF in patients who underwent primary surgery without subsequent adjuvant RT. None of the patients with pathological complete remission (CR) after induction chemotherapy died or experienced LRF., Conclusions: Our study revealed that the outcomes of primary surgery and primary RT in HPV-positive tonsil cancer were similar after adjusting for clinical factors. Primary RT might be considered instead of surgery in patients with advanced pathological T stage. In the case of pathological CR after induction chemotherapy, deintensification for adjuvant RT should be considered., (© 2022. The Author(s).)

Objectives: Unilateral radiation to cervical nodes has been used as a de-escalation strategy in well-lateralized tonsil cancers. The efficacy of this approach with multiple ipsilateral nodes is not established. The study hypothesis was that unilateral radiation for American Joint Committee on Cancer (AJCC)-7 T1-2N2b tonsillar cancer results in a low rate of contralateral nodal failure., Materials and Methods: This study was a retrospective chart review of patients with AJCC-7 T1-2N2b tonsillar cancer from 2 academic institutions who were treated with unilateral radiation. The primary endpoint was the contralateral nodal failure rate. Locoregional control, overall survival, and the need for gastrostomy tube placement were additional endpoints., Results: The study cohort included 66 patients treated between 2005 and 2016. The median follow-up time was 80.9 months; contralateral nodal failure occurred in 2/66 (3.0%) patients at 4.1 and 20.9 months, respectively. Both patients underwent salvage treatment with long-term subsequent survival. Overall locoregional control at both 2 and 5 years was 93.9% and the median duration of control was not reached. Overall survival at 5 years was 92.4%., Conclusions: The use of unilateral radiation for AJCC-7 T1-2N2b tonsillar cancer resulted in low rates of contralateral nodal failure. This outcome demonstrates the safety of considering unilateral radiation treatment in patients with a relatively high ipsilateral nodal burden., Competing Interests: A.F. was supported by the ASTRO-AstraZeneca Radiation Oncology Research Training Fellowship. V.T. was supported in part by Career Development Award IK2 BX004360 from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service and the Dr. Bernard S. Aron Fund. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The primary course of treatment for patients with low- to intermediate-risk tonsil cancer has evolved with a shift toward primary transoral robotic surgery (TORS) or radiation therapy (RT). While favorable outcomes have been reported after deintensification via unilateral TORS or RT (uniRT), comparisons of functional outcomes between these treatments are lacking. We compared clinical outcomes (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST] and feeding tube [FT]) and patient-reported swallowing outcomes (MD Anderson Dysphagia Inventory [MDADI]) based on primary treatment strategy: TORS, uniRT, or bilateral RT (biRT)., Study Design: Secondary analysis of prospective cohort., Setting: Single institution., Methods: The study sample comprised 135 patients with HPV/p16+ T1-T3, N0-2b (American Joint Committee on Cancer, seventh edition), N0-1 (eighth edition) squamous cell carcinoma of the tonsil were sampled from a prospective registry. Modified barium swallow studies graded per DIGEST, FT placement and duration, and MDADI were collected., Results: Baseline DIGEST grade significantly differed among treatment groups, with higher dysphagia prevalence in the TORS group (34%) vs the biRT group (12%, P = .04). No significant group differences were found in DIGEST grade or dysphagia prevalence at subacute and longitudinal time points ( P = .41). Mean MDADI scores were similar among groups at baseline (TORS, 92; uniRT, 93; biRT, 93; P = .90), subacute (TORS, 83; uniRT, 88; biRT, 82; P = .38) and late time points (TORS, 86; uniRT, 86; biRT, 87; P = .99). FT placement and duration significantly differed among primary treatment groups (FT [median days]: TORS, 89% [3]; uniRT, 8% [82]; biRT, 37% [104]; P < .001)., Conclusion: While TORS and uniRT offer optimal functional outcomes related to dysphagia, results suggest that no measurable clinician-graded or patient-reported differences in swallow outcomes exist among these primary treatment strategies and biRT. Aside from baseline differences that drive treatment selection, differences in FT rate and duration by primary treatment strategy likely reflect diverse toxicities beyond dysphagia.

Purpose: The goal of this study was to evaluate disease, survival, and toxic effects after unilateral radiation therapy treatment for tonsillar cancer., Methods and Materials: A retrospective study was performed of patients treated at our institution within the period from 2000 to 2018. Summary statistics were used to assess the cohort by patient characteristics and treatments delivered. The Kaplan-Meier method was used to determine survival outcomes., Results: The cohort comprised 403 patients, including 343 (85%) with clinical and/or radiographic evidence of ipsilateral cervical nodal disease and 181 (45%) with multiple involved nodes. Human papillomavirus was detected in 294 (73%) tumors. Median follow-up time was 5.8 years. Disease relapse was infrequent with local recurrence in 9 (2%) patients, neck recurrence in 13 (3%) patients, and recurrence in the unirradiated contralateral neck in 9 (2%) patients. Five- and 10-year overall survival rates were 94% and 89%, respectively. Gastrostomy tubes were needed in 32 (9%) patients, and no patient had a feeding tube 6 months after therapy., Conclusions: For patients with well-lateralized tonsillar tumors and no clinically evident adenopathy of the contralateral neck, unilateral radiation therapy offers favorable rates of disease outcomes and a relatively low toxicity profile., (Copyright © 2022. Published by Elsevier Inc.)

Background: To evaluate the efficacy and safety of reducing target volume in definitive radiotherapy for HPV-associated tonsil cancer., Methods: A single-institution cohort of 90 patients with human papillomavirus (HPV)-associated tonsil cancer who received definitive radiotherapy with a 5-mm expansion from the gross tumor volume to clinical target volume between 2008 and 2019 were included. The overlapping volume of initial planning target volume and the recurrent tumor was calculated and categorized as one of three failure types: in-field: ≥95%; marginal-field: 50%-94%; and out-field: <50%., Results: With a median follow-up of 59.4 months, the 3-year and 5-year local control rates were 94.4% and 92.8%, respectively. A total of seven local failures were identified, of which 4 (4.4%) were in-field, 2 (2.2%) were marginal-field, and 1 (1.1%) was out-field. Grade 3 acute and late toxicities developed in 30 (33.3%) and 5 (5.6%) patients, respectively., Conclusions: Reducing target volume could be an alternative option for selected patients with HPV-associated tonsil cancer., (© 2022 Wiley Periodicals LLC.)

Fanconi anemia is primarily inherited as an autosomal recessive genetic disorder with common delays in diagnosis and challenging treatments. Fanconi anemia patients have a high risk of developing solid tumors, particularly in the head and neck or anogenital regions. The diagnosis of Fanconi anemia is primarily based on the chromosomal breakage but FA gene sequencing is recommended in all patients with a positive chromosome fragility test. Here, we present a 32-year-old man with advanced tonsil squamous cell carcinoma and fatal toxicity after the first cycle of chemotherapy. No anemia was present. A recent variant mutation if the FANCM gene was detected (c1511&#95;1515delGAGTA (pArg504AsnfsTer29)). Homozygous or double heterozygous pathogenic variants have been reported in FANCM and linked to azoospermia and primary ovarian failure without anemia. Alterations in this gene have also been associated with a genetic predisposition for solid tumors (breast and ovarian cancer) and hematological malignancies (B-cell acute lymphoblastic leukemia). Due to the hypersensitivity of these patients to DNA-damaging agents such as chemotherapy and radiotherapy, surgery is the best treatment option for malignant solid tumors. Dose reductions or alternative regimens of chemotherapy and/or radiotherapy are recommended in FA patients who develop a malignant tumor., (Copyright © 2021. Published by Elsevier Masson SAS.)

Backgroud: Primary tonsil diffuse large B cell lymphoma (PT-DLBCL) is an uncommon disease entity. The role of radiation therapy (RT) in PT-DLBCL is debatable in both the pre- and post- rituximab era. The purpose of this study was to evaluate the treatment outcome and establish a prognostic model in PT-DLBCL based on the Surveillance, Epidemiology, and End Results (SEER) database., Materials and Methods: Data of 1214 PT-DLBCL patients diagnosed between 1975 and 2016 were extracted from SEER 18. The effect of RT was assessed for the entire cohort and subgroups by stages using univariate, multivariate Cox regression analyses and propensity score matching (PSM)., Results: The entire cohort included 1043 patients with early-stage (ES) PT-DLBCL and 171 patients with advanced-stage (AS) disease. A decreasing trend of RT utilization in the ES cohort after 2002 was observed. 47.4% of patients in ES received RT, whereas 25.1% in AS underwent RT. RT significantly improved overall survival in both univariate (P < 0.001) and multivariate (P = 0.002) analyses. PSM analysis further validated the survival advantage of RT (P = 0.002). A nomogram was established to predict the potential survival benefit. Subgroup analysis revealed RT was significantly associated with overall survival in ES patients of PT-DLBCL (P = 0.001) and in the rituximab era (P = 0.001) but not in those with AS disease (P = 0.241)., Conclusions: This population-based study encloses the largest sample of PT-DLBCL to date and demonstrates a favorable survival role of RT in early stages rather than advanced stages. The established nomogram helps to identify high risk patients to improve prognosis., (© 2021. The Author(s).)

Purpose: To compare treatment costs and cost-effectiveness for transoral robotic surgery (TORS) and definitive intensity-modulated radiotherapy (IMRT) in managing early stage tonsil cancer., Materials and Methods: Direct treatment costs for surgery and IMRT were calculated from SEER-Medicare data for a cohort with clinically early stage (cT1/2N0) p16+ tonsillar squamous cell carcinoma from Kaiser Permanente Southern California Health Plan between 2012 and 2017. A Markov decision tree model with a 5-year time horizon was then applied to the cohort which incorporated costs associated with treatment, surveillance, and recurrence., Results: IMRT cost up to $19,000 more (35%) than TORS in direct treatment costs. When input into the Markov model, TORS dominated IMRT with lower cost and better effectiveness over a range of values., Conclusion: TORS is a more cost-effective treatment method than IMRT in early stage (cT1/2N0) tonsil cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

: A 64-year-old man, whose medical history was significant only for locally advanced squamocellular carcinoma of the right palatine tonsil treated with extended neck radiotherapy 9 years before, was evaluated for traumatic cerebral haemorrhage secondary to syncope after a postural change. The selective angiographic study of cerebral vessels was negative. No heart arrhythmias were recorded at ECG monitoring. The 24-h ABPM revealed sudden pressor and depressor episodes during day-time and a reverse dipper pattern during night-time. Noninvasive autonomic nervous system function testing showed supine hypertension and orthostatic hypotension caused by afferent baroreflex failure. According to literature, even if only few cases are described, neck irradiation can be assumed to be the major cause of baroreflex failure. No treatment is currently approved. The patient was treated with a selective beta-blocker (bisoprolol) administered at bedtime. Repeated ABPM after 1 month of therapy showed absence of sudden pressor and depressor episodes and no dipper pattern during night-time.

Objective: One approach to reduce treatment-related morbidity for human papilloma virus (HPV)-associated tonsil cancer is omitting radiotherapy to the contralateral neck. Pathologic risk factors for early contralateral neck disease, however, are poorly understood. We report on the risk contralateral neck failures from the time of pre-operative diagnostic imaging to time of planning for adjuvant radiation in a single institution series of HPV-associated tonsillar cancer patients undergoing surgery followed by radiotherapy (RT)., Methods: Retrospective analysis of 123 patients with T1 - T3 HPV-positive tonsillar squamous cell carcinoma treated between 2010 and 2016 with transoral robotic surgery and selective ipsilateral neck dissection followed by adjuvant RT. Contralateral neck recurrence was classified as the detection of a pathologic node in the contralateral neck prior to initiation of adjuvant RT., Results: Seven patients (5.7%) developed contralateral neck disease/failure between the time of pre-operative diagnostic neck imaging and time of planning of adjuvant radiation. Increased ratio of positive/resected nodes [odds ratio (OR) 1.073, p = 0.005] was significantly associated with increased risk of contralateral neck recurrence, with a trend found for close/positive margins (OR 5.355, p = 0.06), tumor size (OR 2.046, p = 0.09), and total number of nodes positive (OR 1.179, p = 0.062)., Conclusions: Patients who develop very early contralateral neck disease, between completion of ipsilateral neck dissection and the initiation of radiotherapy, have a higher ratio of positive nodes to total nodes resected in the ipsilateral neck. These findings suggest that proper selection of patients for omission of treatment of the contralateral, node-negative neck should be made with this in mind, with future studies needed to document the impact on toxicity and disease outcomes from such an approach., Advances in Knowledge: Pathologic risk factors in the dissected, ipsilateral neck in patients with tonsil cancer may inform the risk of contralateral neck failure. Patient selection for future, prospective efforts to examine sparing of the contralateral neck need to be based with these risk factors in mind.

Purpose: To benchmark and improve, through means of a targeted intervention, the quality of intensity modulated radiation therapy treatment planning for locally advanced head and neck cancer (HNC) in the Netherlands. The short and long-term impact of this intervention was assessed., Methods and Materials: A delineated computed tomography-scan of an oropharynx HNC case was sent to all 15 Dutch radiation therapy centers treating HNC. Aims for planning target volume and organ-at-risk (OAR) dosimetry were established by consensus. Each center generated a treatment plan. In a targeted intervention, OAR sparing of all plans was discussed, and centers with the best OAR sparing shared their planning strategies. Impact of the intervention was assessed by (1) short-term (half a year after intervention) replanning of the original case and (2) long-term (1 and 3 years after intervention) planning of new cases., Results: Benchmarking revealed substantial difference in OAR doses. Initial mean doses were 22 Gy (range, 15-31 Gy), 35 Gy (18-49 Gy), and 37 Gy (20-46 Gy) for the contralateral parotid gland, contralateral submandibular gland, and combined swallowing structures, respectively. Replanning after targeted intervention significantly reduced mean doses and variation, but clinically relevant differences still remained: 18 Gy (14-22 Gy), 28 Gy (17-45 Gy), and 29 Gy (18-39 Gy), respectively. One and 3 years later the variation remained stable., Conclusions: Despite many years of HNC intensity modulated radiation therapy experience, initial treatment plans showed surprisingly large variations. The simple targeted intervention used in this analysis improved OAR sparing, and its impact was durable; however, fairly large dose differences still continue to exist. Additional work is needed to understand these variations and to minimize them. A national radiation oncology platform can be instrumental for developing and maintaining high-quality planning protocols., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Radiotherapy (RT), the main treatment for patients with head and neck cancer, can lead to dental complications., Methods: We identified 244 patients with squamous cell carcinoma of the tonsil treated with RT from 2004 to 2013. For each patient, we contoured the 10 tooth-bearing regions and calculated the radiation dose (gray, Gy) to each region. From this data set, we built two predictive models to determine the expected maximum radiation dose, one for the non-molar regions and another for the molar regions., Results: For the non-molars, the final model included location, T-classification, and overall stage, with a median absolute prediction error of 7.0 Gy. For the molars, the final model included location, T-classification, overall stage, and treatment year, with a median absolute error of 6.0 Gy., Conclusions: Our current model offers a good estimation of the maximum radiation dose delivered to different regions of the jaw; future work will independently validate these models., (© 2019 Wiley Periodicals, Inc.)

Background: Radiation-therapy (RT) induces mucositis, a clinically challenging condition with limited prophylactic interventions and no predictive tests. In this pilot study, we applied global gene-expression analysis on serial human oral mucosa tissue and blood cells from patients with tonsil squamous cell cancer (TSCC) to identify genes involved in mucositis pathogenesis., Methods and Findings: Eight patients with TSCC each provided consecutive buccal biopsies and blood cells before, after 7 days of RT treatment, and 20 days following RT. We monitored clinical mucositis and performed gene-expression analysis on tissue samples. We obtained control tissue from nine healthy individuals. After RT, expression was upregulated in apoptosis inducer and inhibitor genes, EDA2R and MDM2, and in POLH, a DNA-repair polymerase. Expression was downregulated in six members of the histone cluster family, e.g., HIST1H3B. Gene expression related to proliferation and differentiation was altered, including MKI67 (downregulated), which encodes the Ki-67-proliferation marker, and KRT16 (upregulated), which encodes keratin16. These alterations were not associated with the clinical mucositis grade. However, the expression of LY6G6C, which encodes a surface immunoregulatory protein, was upregulated before treatment in three cases of clinical none/mild mucositis, but not in four cases of ulcerative mucositis., Conclusion: RT caused molecular changes related to apoptosis, DNA-damage, DNA-repair, and proliferation without a correlation to the severity of clinical mucositis. LY6G6C may be a potential protective biomarker for ulcerative mucositis. Based on these results, our study model of consecutive human biopsies will be useful in designing a prospective clinical validation trial to characterize molecular mucositis and identify predictive biomarkers.

Background: The authors hypothesized that unilateral intensity-modulated radiotherapy (IMRT) would decrease toxicity compared with bilateral IMRT for patients with lateralized palatine tonsillar cancer and a neck classification of N0 to N2b, with similar oncological outcomes., Methods: A total of 154 patients were treated with postoperative IMRT from 1997 through 2013. Data were collected prospectively from 2005 to 2013 and retrospectively collected before 2005. Of those patients with lateralized primary and N0 to N2b disease, 48 received unilateral IMRT (group 1) and 59 received bilateral IMRT (group 2); a total of 47 patients had nonlateralized primary or N2c to N3 disease and received bilateral IMRT (group 3)., Results: The median follow-up was 5.5 years. The 5-year locoregional control rates were similar in group 1, group 2, and group 3 (100%, 96%, and 94%, respectively; pooled comparison: P = .39 and group 1 vs group 2 comparison: P = .19). The 5-year overall survival rates were similar in group 1, group 2, and group 3 (85%, 79%, and 76%, respectively; pooled comparison: P = .60 and group 1 vs group 2 comparison: P = .25). There were no contralateral neck recurrences noted among unilaterally treated patients. Unilateral IMRT reduced acute toxicity and improved patient-reported quality of life compared with bilateral IMRT., Conclusions: Unilateral IMRT appears to reduce acute toxicity and achieves oncological outcomes similar to those of bilateral IMRT in selected patients with lateralized palatine tonsillar cancer with a neck classification of N0 to N2b. Cancer 2017;123:4594-4607. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose: To determine the risk of contralateral nodal failure following ipsilateral radiotherapy in a series of patients with node-positive tonsillar squamous cell carcinoma., Methods: Retrospective review was used to identify 34 patients with well-lateralized node-positive tonsillar squamous cell carcinoma treated with definitive or adjuvant radiation to the primary site and ipsilateral neck between 2005 and 2015. Contralateral nodal failure, locoregional recurrence, distant metastasis, and overall survival were calculated using actuarial and/or cumulative incidence statistics., Results: At last follow-up, contralateral nodal failure was only observed in 1 patient (3%) with N1 disease. At median follow-up of 34 months for surviving patients, the 3-year overall survival probability was 87%, and the 3 year cumulative incidences of locoregional failure and distant metastasis were 6.5% and 7.2%, respectively. No disease-free patient was permanently gastrostomy-dependent., Conclusion: Ipsilateral radiation treatment with IMRT is effective in node-positive patients with well-lateralized tonsillar cancer, resulting in a low risk of contralateral regional recurrence, even in patients with N2b disease., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: The impact of postoperative ipsilateral neck radiotherapy (INRT) versus bilateral neck radiotherapy (BNRT) on the clinical outcomes of patients with tonsillar squamous cell carcinoma was analyzed retrospectively., Materials and Methods: Between October 2001 and June 2012, 241 patients with T1-2 and N0-N2b tonsillar carcinoma from 16 institutes underwent postoperative INRT (n=84) or BNRT (n=157) following a tonsillectomy. Seventy patients were identified from each group by propensity score matching and compared in terms of the overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates calculated using the Kaplan-Meier method with a log-rank test., Results: The median follow-up was 55 months (range, 3 to 133 months). The survival outcomes in the INRT and BNRT groups were similar: 5-year OS (92.8% vs. 94.0%, p=0.985), DFS (80.5% vs. 94.2%. p=0.085), LRRFS (88.1% vs. 97.1%, p=0.083), and DMFS (92.7% vs. 97.0%, p=0.370). Subgroup analysis revealed no contralateral neck recurrence in 61 patients with T1-2N0-2a regardless of the treatment groups. For 79 patients with N2b, contralateral neck recurrence was more common in the INRT group than in the BNRT group (7.9% vs. 0.0%), but the difference was not significant (p=0.107). The overall grade ≥ 2 toxicities were lower in the INRT group: acute (45.7% vs. 74.3%, p=0.001) and late (4.3% vs. 31.4%, p < 0.001), respectively., Conclusion: INRT is an attractive strategy for patients with T1-2N0-2a tonsillar carcinoma compared to BNRT. For patients with N2b, there was a small risk of contralateral neck recurrence when treated with INRT, but its impact on the OS was limited with successful salvage treatment.

To analyze the medical literature devoted to work-up, epidemiology, local control, survival, complications and sequelae after conservative treatment for early-stage squamous cell carcinoma of the tonsillar region. An analysis of the PubMed (1975-2016) database was performed using the following keywords and associations: "tonsil/tonsillar region/oropharynx" AND "squamous cell carcinoma" AND "early-stage (I-II; T1-2N0M0)" AND "radiation therapy/radiotherapy" OR "conservative surgery/oropharyngectomy/transoral surgery/radical tonsillectomy". The search retrieved 10 retrospective series documenting local control and/or survival in series with more than 50 cases and a minimum 2 years' follow-up after conservative treatment; no prospective studies, meta-analyses and/or Cochrane analyses were found. Magnetic resonance imaging is the key radiological exam for local extension assessment. Human papilloma virus infection (HPV) is a risk factor that must be screened for systematically, since it induces tumoral radio-sensitivity and increases the risk of specific synchronous and metachronous second primaries. Whatever conservative treatment used, local control and survival rates higher than 85% were achieved. Implementing intensity-modulated radiation therapy reduced the incidence and severity of radiation-related complications and sequelae. Transoral surgery yielded very low morbidity/mortality rates, enabled association to ipsilateral neck dissection, and allowed radiation therapy to be reserved for the management of metachronous second primaries. Transoral surgery appeared to be the first-line option in the majority of cases. Lifetime follow-up adapted to HPV status is mandatory. The development of HPV vaccination does not mean that campaigns against smoking and alcohol abuse are of diminished importance., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Purpose: To report the outcome of ipsilateral radiation therapy (RT) in human papillomavirus (HPV)-positive (HPV+) patients and HPV-negative (HPV-) patients with T1-T2N0-N2b tonsillar cancer treated 25 years after our initial historical cohort., Methods and Materials: Patients with T1-T2N0-N2b tonsillar cancer who received ipsilateral RT or bilateral RT between 1999 and 2014 were reviewed. Overall survival (OS), local control (LC), regional control (RC), and grade 3 to 4 late toxicity (LT) were compared between ipsilateral RT and bilateral RT within HPV+ and HPV- patients, separately., Results: HPV status was ascertained in 379/427 (88%) consecutive patients (ipsilateral RT: 62 HPV+, 34 HPV-; bilateral RT: 240 HPV+ 240, 41 HPV-). The proportion of ipsilateral RT by N category for HPV+ and HPV- patients were as follows: N0: 24/37 (65%) versus 28/48 (74%); N1: 21/49 (43%) versus 4/9 (44%); N2a: 10/39 (26%) versus 1/4 (25%); and N2b: 7/177 (4%) versus 1/24 (4%), respectively. Of the patients receiving ipsilateral RT, 94/96 (98%) were treated with RT alone. The median follow-up time was 5.03 years. The respective 5-year rates of OS, LC, RC, and LT were similar between ipsilateral RT and bilateral RT for the HPV+ patients (OS: 89% vs 87%, P=.55; LC: 97% vs 98%, P=.65; RC: 98% vs 97%, P=.27; LT: 17% vs 12%, P=.83) and HPV- patients (OS: 63% vs 48%, P=.27; LC: 90% vs 80%, P=.19; RC: 94% vs 83%, P=.14; LT: 15% vs 22%, P=.36). Of the 96 patients receiving ipsilateral RT, contralateral neck failure (CNF) occurred in 1/52 HPV+ patients and 1/34 HPV- patients. The 5-year CNF rates were 2% (95% CI: 1-9) (HPV+: 2% [0-14]; HPV-: 3% [0-21], P=.66). Five local failures (2 HPV+; 3 HPV-) and no distant failures were seen. The 5-year rates of LC, RC, and LT were 97% versus 90% (P=.24), 98% versus 94% (P=.25), and 18% versus 15% (P=.75) for the HPV+ and HPV- cohorts, respectively. Osteoradionecrosis occurred in 9 patients: 6/47 (13%) treated with conventional RT and 3/49 (6%) with intensity modulated RT (P=.32)., Conclusion: Ipsilateral radiation to selected patients with T1-T2N0-N2b tonsillar cancer results in equally excellent outcomes regardless of tumor HPV status., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Trans-oral robotic surgery (TORS) followed by adjuvant radiation therapy (RT) is becoming popular in treating node-positive tonsillar squamous cell carcinoma (SCC). One potential benefit is eliminating irradiation of the primary site when the tumor is widely resected, and targeting the neck only. This study assessed whether omitting the tumor bed provides any dosimetric or clinical advantage., Methods and Materials: We identified 21 patients with primary tonsillar SCC that were treated with TORS followed by RT to the ipsilateral neck and primary (N+P) site. We subsequently replanned each case to allow target coverage to the neck only, excluding the tumor bed. For each case, we created 2 plans: neck only (NO) and N+P. Additionally, we identified patients (n = 7) with primary SCC tonsil who did receive NO irradiation to compare their dosimetry and toxicity profile with those treated to both the primary site and ipsilateral neck. Contralateral neck radiation was not administered in any of these cases., Results: Despite excluding the primary site in the NO plans, the mean dose to the tumor bed was high: 53.9 Gy. The only significant differences in omitting the primary site were lower doses to the oral cavity, 29.8 Gy in NO plan versus 34.6 Gy in N+P plan, P = .002, and superior constrictors, 42.9 Gy in NO plan versus 46.1 Gy in N+P plan, P = .01. No appreciable differences in toxicities were noted in the limited cohort treated with NO irradiation., Conclusions: Sparing the primary site after TORS in node-positive tonsillar SCC does not appear to provide any significant dosimetric or clinical advantage. Furthermore, the tumor bed receives a significant but potentially subtherapeutic dose, limiting options for irradiation in a salvage setting. At this time, we do not recommend omitting the tumor bed from the radiation target volume following TORS., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine the rate of contralateral neck recurrence after surgery and unilateral neck radiotherapy, for lateralized tonsillar cancers with ipsilateral neck disease, in order to inform future clinical trial protocols for this disease., Methods: Patients with lateralized tonsillar squamous carcinoma (T1-T2, N0-N2b), treated with surgery and unilateral adjuvant radiotherapy in a single United Kingdom center were retrospectively identified. Rates of recurrence in the contralateral, unirradiated neck were analyzed, together with survival and toxicity data., Results: Of 81 patients included, after a median follow-up of 5.7 years, no contralateral recurrences were identified. Five-year overall survival, progression-free survival, and locoregional control were 91.0%, 93.0%, and 95.4%, respectively., Conclusion: Unilateral radiotherapy is an effective and safe treatment option for the postoperative management of lateralized tonsillar cancers, even in patients with N2b disease, and should be recommended in future clinical trial protocols. © 2016 Wiley Periodicals, Inc. Head Neck 39: 17-23, 2017., (© 2016 Wiley Periodicals, Inc.)

Purpose: To assess the impact of radiation treatment time (RTT) in head and neck cancers on overall survival (OS) in the era of chemoradiation., Methods and Materials: Patients with diagnoses of tongue, hypopharynx, larynx, oropharynx, or tonsil cancer were identified by use of the National Cancer Database. RTT was defined as date of first radiation treatment to date of last radiation treatment. In the definitive setting, prolonged RTT was defined as >56 days, accelerated RTT was defined as <47 days, and standard RTT was defined as 47 to 56 days. In the postoperative setting, prolonged RTT was defined as >49 days, accelerated RTT was defined as <40 days, and standard RTT was defined as 40 to 49 days. We used χ 2 tests to identify predictors of RTT. The Kaplan-Meier method was used to compare OS among groups. Cox proportional hazards model was used for OS analysis in patients with known comorbidity status., Results: 19,531 patients were included; 12,987 (67%) had a standard RTT, 4,369 (34%) had an accelerated RTT, and 2,165 (11%) had a prolonged RTT. On multivariable analysis, accelerated RTT (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.73-0.97) was associated with an improved OS, and prolonged RTT (HR 1.25; 95% CI 1.14-1.37) was associated with a worse OS relative to standard RTT. When the 9,200 (47%) patients receiving definitive concurrent chemoradiation were examined, prolonged RTT (HR 1.29; 95% CI 1.11-1.50) was associated with a worse OS relative to standard RTT, whereas there was no significant association between accelerated RTT and OS (HR 0.76; 95% CI 0.57-1.01)., Conclusion: Prolonged RTT is associated with worse OS in patients receiving radiation therapy for head and neck cancer, even in the setting of chemoradiation. Expeditious completion of radiation should continue to be a quality metric for the management of head and neck malignancies., Competing Interests: None, (Copyright © 2016 Elsevier Inc. All rights reserved.)

Carcinoma tonsil with visceral metastasis is a rare entity, and cutaneous metastasis is seen even more infrequently. We present a case of a 55-year-old male with carcinoma tonsil having received concurrent chemo radiotherapy, presenting with multiple cutaneous metastases to the scalp and thigh. To the best of our knowledge, till date only two similar cases of carcinoma tonsil with cutaneous metastasis have been reported in the English literature., (Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.)

This study is aimed at updating our institution's experience with definitive radiotherapy (RT) for squamous cell carcinoma of the tonsil. We reviewed 531 patients treated between 1983 and 2012 with definitive RT for squamous cell carcinoma of the tonsil. Of these, 179 patients were treated with either induction (n = 19) or concomitant (n = 160) chemotherapy. Planned neck dissection was performed on 217 patients: unilaterally in 199 and bilaterally in 18 patients. Median follow-up was 5.2 years for all patients (range 0.1-31.6 years) and 8.2 years for living patients (range 1.9-31.6 years). The 5-year local control rates by T stage were as follows: T1, 94 %; T2, 87 %; T3 79 %; T4, 70 %; and overall, 83 %. Multivariate analysis revealed that local control was significantly influenced by T stage and neck dissection. The 5-year cause-specific survival rates by overall stage were as follows: I, 94 %; II, 88 %; III, 87 %; IVA, 75 %; IVB, 52 %; and overall, 78 %. Multivariate analysis revealed that cause-specific survival was significantly influenced by T stage, N stage, overall stage, fractionation, neck dissection, sex, and ethnicity. Of 77 patients treated with ipsilateral fields only, contralateral neck failure occurred in 1 %. The rate of severe complications was 12 %. Definitive RT for patients with tonsillar squamous cell carcinoma provides control rates equivalent to other modalities with a comparatively low incidence of late complications. Patients with anterior tonsillar pillar or tonsillar fossa primaries that are well lateralized with no base of tongue or soft palate extension may be treated with ipsilateral fields.

The objective of the study is to perform a national survey of practices in early-stage squamous cell carcinoma (SCC) of the oropharynx (base of tongue and tonsils) targeting surgical and non-surgical procedures in France. A questionnaire concerning practices in surgery, radiotherapy, HPV screening, and two clinical cases were sent to all centers participating in the French Head and Neck Oncology Society, and to public hospitals listed as authorized to treat head and neck cancer according to the French National Cancer Institute (INCa). Sixty-four teams comprising almost all the University Hospitals and most of the Comprehensive Cancer Centers completed the survey questionnaire and responded to the clinical cases. Surgical and radiotherapy strategies were used in similar measure for early-stage SCC of the base of the tongue while tonsil lesions were mainly treated with surgery. The main arguments were disease control for the teams offering patients surgery, and functional results for those offering radiotherapy. However, concomitant chemoradiotherapy was chosen more frequently than radiotherapy alone in early-stage SCC of the base of tongue. Age and tobacco-alcohol addiction were decisive criteria in decision making for the majority of the teams. French oncology teams offered surgical and radiotherapy strategies in similar measure to treat early-stage SCC of the oropharynx (base of tongue and tonsils) as well as a high rate of multimodality therapy. Decision making was guided by the desire to achieve oncologic results adapted to the patient and his age, as well as functional preservation taking into account life expectancy.

The purpose of this study is to update our institution's experience with ipsilateral radiation therapy (RT) for squamous cell carcinoma of the tonsillar area. Outcome study of 76 patients treated between 1984 and 2012 with ipsilateral RT for squamous cell carcinoma of the tonsil. Patients had either cT1 (n = 41, 54 %) or cT2 (n = 35, 46 %) primaries and cN0 (n = 27, 36 %), cN1 (n = 15, 20 %), cN2a (n = 8, 11 %), or cN2b (n = 26, 34 %) nodal disease. Of these, 32 (42 %) patients underwent a planned neck dissection and 21 (28 %) patients received concomitant chemotherapy. Median follow-up for all patients was 7.1 years (range 0.1-27.2) and 7.8 years (range 2.1-27.2 years) for living patients. The 2- and 5-year control and survival rates were as follows: local control, 98.6 and 96.9 %; local-regional control 95.8 and 92.6 %; cause-specific survival 95.9 and 93.1 %; and overall survival, 92.1 and 83.8 %. One patient failed in the contralateral, non-radiated neck 3 years after primary treatment. Univariate analysis revealed that overall survival was significantly influenced by whether the patient had a primary tumor in the anterior tonsillar pillar versus the tonsillar fossa with the latter performing better. The incidence of severe late complications was 16 %. Ipsilateral RT for patients with squamous cell carcinoma of the anterior tonsillar pillar or tonsillar fossa with no base of tongue or soft palate extension is an efficacious treatment that provides excellent control rates with a relatively low incidence of late complications.

Aim: The aim of this study was to investigate potential advantages and disadvantages of three-dimensional conformal radiotherapy (3DCRT), multiple fixed-field intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) in terms of dose to the planning target volume (PTV), organs at risk (OARs) and normal tissue complication probability (NTCP) for delivering ipsilateral radiotherapy., Materials and Methods: 3DCRT, IMRT and VMAT were compared in patients with well-lateralised primary tonsillar cancers who underwent primary radical ipsilateral radiotherapy. The following parameters were compared: conformity index (CI); homogeneity index (HI); dose-volume histograms (DVHs) of PTVs and OARs; NTCP, risk of radiation-induced cancer and dose accumulation during treatment., Results: IMRT and VMAT were superior to 3DCRT in terms of CI, HI and dose to the target volumes, as well as mandible and dose accumulation robustness. The techniques were equivalent in terms of dose and NTCP for the contralateral oral cavity, contralateral submandibular gland and mandible, when specific dose constraint objectives were used on the oral cavity volume. Although the volume of normal tissue exposed to low-dose radiation was significantly higher with IMRT and VMAT, the risk of radiation-induced secondary malignancy was dependant on the mathematical model used., Conclusion: This study demonstrates the superiority of IMRT/VMAT techniques over 3DCRT in terms of dose homogeneity, conformity and consistent dose delivery to the PTV throughout the course of treatment in patients with lateralised oropharyngeal cancers. Dosimetry and NTCP calculations show that these techniques are equivalent to 3DCRT with regard to the risk of acute mucositis when specific dose constraint objectives were used on the contralateral oral cavity OAR.

Background: A questionnaire-based study was conducted to assess long-term patient reported outcomes (PROs) following definitive IMRT-based treatment for early stage carcinomas of the tonsillar fossa., Methods: Participants had received IMRT with or without systemic therapy for squamous carcinoma of the tonsillar fossa (T1-2 and N0-2b) with a minimum follow-up of 2years. Patients completed a validated head and neck cancer-specific PRO instrument, the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Symptoms were compared between treatment groups of interest and overall symptom burden was evaluated., Results: Of 139 participants analyzed, 51% had received ipsilateral neck IMRT, and 62% single modality IMRT alone (no systemic therapy). There were no differences in mean severity ratings for the top-ranked individual symptoms or symptom interference for those treated with bilateral versus ipsilateral neck IMRT alone. However, 40% of those treated with bilateral versus 25% of those treated with ipsilateral neck RT alone reported moderate-to-severe levels of dry mouth (p=0.03). Fatigue, numbness/tingling, and constipation were rated more severe for those who had received systemic therapy (p<0.05 for each), but absolute differences were small. Overall, 51% had no more than mild symptom ratings across all 22 symptoms assessed., Conclusions: The long-term patient reported symptom profile in this cohort of tonsil cancer survivors treated with definitive IMRT-based treatment showed a majority of patients with no more than mild symptoms, low symptom interference, and provides an opportunity for future comparison studies with other treatment approaches., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The purpose of this study was to systematically monitor anatomic variations and their dosimetric consequences during intensity modulated radiation therapy (IMRT) for head and neck (H&N) cancer by using a graphics processing unit (GPU)-based deformable image registration (DIR) framework., Methods and Materials: Eleven IMRT H&N patients undergoing IMRT with daily megavoltage computed tomography (CT) and weekly kilovoltage CT (kVCT) scans were included in this analysis. Pretreatment kVCTs were automatically registered with their corresponding planning CTs through a GPU-based DIR framework. The deformation of each contoured structure in the H&N region was computed to account for nonrigid change in the patient setup. The Jacobian determinant of the planning target volumes and the surrounding critical structures were used to quantify anatomical volume changes. The actual delivered dose was calculated accounting for the organ deformation. The dose distribution uncertainties due to registration errors were estimated using a landmark-based gamma evaluation., Results: Dramatic interfractional anatomic changes were observed. During the treatment course of 6 to 7 weeks, the parotid gland volumes changed up to 34.7%, and the center-of-mass displacement of the 2 parotid glands varied in the range of 0.9 to 8.8 mm. For the primary treatment volume, the cumulative minimum and mean and equivalent uniform doses assessed by the weekly kVCTs were lower than the planned doses by up to 14.9% (P=.14), 2% (P=.39), and 7.3% (P=.05), respectively. The cumulative mean doses were significantly higher than the planned dose for the left parotid (P=.03) and right parotid glands (P=.006). The computation including DIR and dose accumulation was ultrafast (∼45 seconds) with registration accuracy at the subvoxel level., Conclusions: A systematic analysis of anatomic variations in the H&N region and their dosimetric consequences is critical in improving treatment efficacy. Nearly real-time assessment of anatomic and dosimetric variations is feasible using the GPU-based DIR framework. Clinical implementation of this technology may enable timely plan adaptation and improved outcome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To update the outcomes of an institutional clinical management approach using ipsilateral neck radiotherapy in the treatment of node-positive squamous cell carcinoma of the tonsil with a well-lateralized primary lesion., Methods and Materials: Between August 2003 and April 2014, 61 consecutive patients with ipsilateral node-positive squamous cell carcinoma of the tonsil without involvement of the base of the tongue or midline soft palate were treated at a community hospital-based cancer center with radiotherapy to the primary site and ipsilateral neck. Overall survival, disease-free survival and freedom from contralateral failure were calculated., Results: Median follow up was 37.2months (range 4-121months). Freedom from contralateral nodal failure at 5years was 98% with one contralateral nodal failure noted. The patient underwent a salvage neck dissection and was treated with post-operative radiotherapy with no evidence of disease to date. 5-year overall survival (OS) was 92.4% and 5year disease-free survival (DFS) was 86.7%., Conclusions: This represents the single largest series reported from a community hospital-based cancer center in which lateralized tonsil cancers with N+ disease were treated with ipsilateral neck radiotherapy. In this carefully selected cohort of patients with well-lateralized tonsil cancers, the risk of contralateral nodal failure appears to be <5%, suggesting that prophylactic radiation of the contralateral neck may not be necessary. Future planned studies will focus on prospectively selecting subgroups of patients eligible for treatment de-intensification as survivorship issues in excellent prognosis HPV positive patients are increasingly becoming relevant., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to report the long-term outcome of patients with squamous cell cancer (SCC) of the tonsil managed by surgery followed by postoperative radiotherapy (PORT)., Methods: Eighty-eight patients treated between 1985 and 2005 were analyzed. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by univariate and multivariate analysis., Results: Forty-eight percent of patients had T3 to T4 disease and 75% had a positive neck. Five-year OS, DSS, and RFS were 66%, 82%, and 80%, respectively. The status of the neck was not predictive of outcome (DSS 80% for N0 vs 82% for N+; p = .97). Lymphovascular invasion was an independent predictor of OS, DSS, and RFS on multivariate analysis., Conclusion: Lymphovascular invasion but not pathological stage of the neck is an independent predictor of outcome in patients with tonsillar SCC., (© 2014 Wiley Periodicals, Inc.)

The treatment of neuropathic pain is a medical challenge. The responsiveness to the different classes of drugs is often unsatisfactory and frequently associated to a wide range of side effects. International guidelines suggest for the "localized" neuropathic pain the topical treatment with 5% lidocaine medicated plaster, alone or associated to systemic drugs, as the first choice since its favorable efficacy and tolerability profile. Many clinical experiences support the rationale for using 5% lidocaine medicated plaster in different kinds of localized neuropathic pain, such as postherpetic and trigeminal neuralgia, compressive syndromes, painful diabetic polyneuropathy and pain secondary to trauma or surgical interventions. This paper reports a series of clinical cases whose heterogeneity suggests the wide burden of applicability of the topical 5% lidocaine, either alone and associated to systemic drugs. All the described conditions were characterized by a highly intense pain, not adequately controlled by actual medications, which improved after the use of topical lidocaine. The good response to lidocaine allowed the reduction, of even the withdrawal, of concurrent drugs and improved the patients' quality of life.

A 66-year-old man with a history of squamous cell carcinoma of the right tonsil presented to the emergency department with two life-threatening episodes of haemoptysis 9 months after completion of chemoradiation. He was evaluated to rule out recurrent malignancy, and was determined to have osteoradionecrosis of his hyoid bone that had led to an oropharyngeal fistula. Given the proximity to branches of the external carotid, he was offered tracheostomy and resection of the protruding necrotic bone with ultrasonic bone aspirator, which was placed down the shaft of the laryngoscope to minimise damage to adjacent structures. He tolerated the procedure well with complete resolution of exposed bone on follow-up laryngoscopy., (2014 BMJ Publishing Group Ltd.)

Background: Ipsilateral radiotherapy is an established technique for treating well-lateralised tonsillar tumours. Concerns exist regarding the risk of contralateral nodal failure, particularly in patients with ipsilateral nodal involvement at presentation. In this study, we retrospectively reviewed the clinical outcomes of patients treated with ipsilateral radiotherapy aiming to identify factors that predispose to a higher risk of contralateral nodal recurrence., Methods: Retrospective case note review of all patients with tonsillar cancer who were treated using ipsilateral radiotherapy between September 1995 and September 2011 was performed. Demographics, T and N stage, involvement of soft palate and/or tongue base, presence of extra-capsular spread (ECS) and treatment details were recorded. Kaplan-Meier curves for treatment outcomes were generated., Results: A total of 136 patients were identified. Median follow-up was 4.2years. Twelve (9%) patients had loco-regional recurrence. Eight patients (6%) had contralateral recurrence. N2b disease, ECS and number of pack-years of smoking were associated with contralateral nodal recurrence. Five-year overall survival was 89%, loco-regional disease-free survival 90%, disease-free survival 86% and distal recurrence-free survival 96%., Conclusion: N2b disease, ECS and a greater than 10 pack-year smoking history are risk factors for contralateral nodal recurrence in well-lateralised tonsillar cancers. Prophylactic irradiation of the contralateral neck should be recommended in this group of patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Evaluation of the efficacy and toxicity of split-course accelerated hyperfractionated irradiation (CHA-CHA) as a sole treatment for advanced head and neck (H&N) cancer patients., Methods: We enrolled 101 patients (39 in CHA-CHA and 37 in conventional (Conv.) arm completed the treatment). The CHA-CHA arm patients were irradiated twice a day, 7 days a week, using a fraction dose (fd) of 1.6 Gy up to 64 Gy with an 8-day gap in midterm. Patients in the control (Conv.) arm group were irradiated with a fd of 2 Gy, five times a week to a total dose of 72-74 Gy in the overall treatment time of 50-53 days. Quality of life (QOL) and acute mucosal reaction were evaluated during radiotherapy (RT). After RT, we followed the effect of treatment, QOL, performance status and adverse effects of radiation. For statistical analysis mainly a hierarchical multilevel modelling was used., Results: QOL was most deteriorated in the CHA-CHA arm; the CHA-CHA scheme also caused a relatively stronger acute injury. There were no significant differences in late adverse effects. In the CHA-CHA arm in 35% and in Conv. arm in 30% of patients, disease was controlled during follow-up. Tumour regression 1 year after the treatment was significantly better in the CHA-CHA arm. However, the overall survival rate analysis did not show significant difference between both arms., Conclusion: Despite differences in treatment results, we cannot conclude that split-course accelerated hyperfractionated irradiation is superior to conventionally fractionated RT as a sole treatment for advanced H&N cancer patients., Advances in Knowledge: Obtained results in the context of published data support the statement that altered fractionations alone do not give an advantage for advanced H&N cancer patients.