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PURPOSE: To explore for fatigue-related regions of interest and the radiotherapy (RT) dose-fatigue relationship in nasopharyngeal cancer (NPC) survivors. METHODS: Eighty disease-free NPC survivors completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN) after RT. Fatigue was evaluated by the MDASI-HN fatigue item (MDASI-HN-F) and Common Terminology Criteria for Adverse Events v3.0 (CTC-AE), between 6 and 36 months after RT to determine the presence of chronic fatigue. Skull base MRIs and planning CT/RT dose were retrievable for 56 patients. Dosimetric data were extracted for 10 MRI-defined potential fatigue at-risk structures (FARS): brainstem (BS), pituitary gland (PG), hypothalamus (HT), basal ganglia, internal capsule, pineal gland, sub-thalamic nuclei, thalamus, substantia nigra, and hippocampus (HC). Recursive partitioning analysis (RPA) were used to identify dose-volume effects associated with chronic fatigue. RESULTS: 56 pts formed the cohort. Thirty patients (54%) reported any fatigue per MDASI-HN-F. Thirty-three pts (59%) had any fatigue by CTC-AE. The maximum point doses (Dmax) for PG, BS, HC, and HT were numerically higher in patients with fatigue. Dmax and Dmean of the PG were significantly higher in patients with chronic fatigue, p ≤ 0.01. A dose-volume threshold of PG V52Gy ≥16% (Logworth 2.4, AUC 0.7) was identified on RPA, and potential sensitivity to the PG doses was observed in younger patients (< 53 years-old). CONCLUSION: A dose-fatigue relationship was identified for the pituitary gland, both patient-reported and observer ratings. We recommend limiting the Dmax of PG to

Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefit of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Intensity modulated proton therapy (IMPT), also known as “pencil beam proton therapy,” is a sophisticated mode of proton therapy that is analogous to IMRT and an active area of investigation in cancer care. Multifield optimization IMPT allows for high quality plans that can target superficially located HNCs as well as large neck volumes while significantly reducing integral doses. Several dosimetric studies have demonstrated the superiority of IMPT over IMRT to improve dose sparing of nearby organs such as the larynx, salivary glands, and esophagus. Evidence of the clinical translation of these dosimetric advantages has been demonstrated with documented toxicity reductions (such as decreased feeding tube dependency) after IMPT for patients with HNCs. While there are relative challenges to IMPT planning that exist today such as particle range uncertainties and high sensitivity to anatomical changes, ongoing investigations in image-guidance techniques and robust optimization methods are promising. A systematic approach towards utilizing IMPT and additional prospective studies are also necessary in order to more accurately estimate the clinical benefit of IMPT over IMRT and passive proton therapy on a case-by-case basis for patients with sub-site specific HNCs.

Summary Background Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with cetuximab—an antibody against the epidermal growth factor receptor—can preserve high survival and reduce treatment toxicity is unknown. We investigated whether cetuximab would maintain a high proportion of patient survival and reduce acute and late toxicity. Methods RTOG 1016 was a randomised, multicentre, non-inferiority trial at 182 health-care centres in the USA and Canada. Eligibility criteria included histologically confirmed HPV-positive oropharyngeal carcinoma; American Joint Committee on Cancer 7th edition clinical categories T1–T2, N2a–N3 M0 or T3–T4, N0–N3 M0; Zubrod performance status 0 or 1; age at least 18 years; and adequate bone marrow, hepatic, and renal function. We randomly assigned patients (1:1) to receive either radiotherapy plus cetuximab or radiotherapy plus cisplatin. Randomisation was balanced by using randomly permuted blocks, and patients were stratified by T category (T1–T2 vs T3–T4), N category (N0–N2a vs N2b–N3), Zubrod performance status (0 vs 1), and tobacco smoking history (≤10 pack-years vs >10 pack-years). Patients were assigned to receive either intravenous cetuximab at a loading dose of 400 mg/m2 5–7 days before radiotherapy initiation, followed by cetuximab 250 mg/m2 weekly for seven doses (total 2150 mg/m2), or cisplatin 100 mg/m2 on days 1 and 22 of radiotherapy (total 200 mg/m2). All patients received accelerated intensity-modulated radiotherapy delivered at 70 Gy in 35 fractions over 6 weeks at six fractions per week (with two fractions given on one day, at least 6 h apart). The primary endpoint was overall survival, defined as time from randomisation to death from any cause, with non-inferiority margin 1·45. Primary analysis was based on the modified intention-to-treat approach, whereby all patients meeting eligibility criteria are included. This study is registered with ClinicalTrials.gov, number NCT01302834. Findings Between June 9, 2011, and July 31, 2014, 987 patients were enrolled, of whom 849 were randomly assigned to receive radiotherapy plus cetuximab (n=425) or radiotherapy plus cisplatin (n=424). 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were subsequently eligible. After median follow-up duration of 4·5 years, radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival (hazard ratio [HR] 1·45, one-sided 95% upper CI 1·94; p=0·5056 for non-inferiority; one-sided log-rank p=0·0163). Estimated 5-year overall survival was 77·9% (95% CI 73·4–82·5) in the cetuximab group versus 84·6% (80·6–88·6) in the cisplatin group. Progression-free survival was significantly lower in the cetuximab group compared with the cisplatin group (HR 1·72, 95% CI 1·29–2·29; p=0·0002; 5-year progression-free survival 67·3%, 95% CI 62·4–72·2 vs 78·4%, 73·8–83·0), and locoregional failure was significantly higher in the cetuximab group compared with the cisplatin group (HR 2·05, 95% CI 1·35–3·10; 5-year proportions 17·3%, 95% CI 13·7–21·4 vs 9·9%, 6·9–13·6). Proportions of acute moderate to severe toxicity (77·4%, 95% CI 73·0–81·5 vs 81·7%, 77·5–85·3; p=0·1586) and late moderate to severe toxicity (16·5%, 95% CI 12·9–20·7 vs 20·4%, 16·4–24·8; p=0·1904) were similar between the cetuximab and cisplatin groups. Interpretation For patients with HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab showed inferior overall survival and progression-free survival compared with radiotherapy plus cisplatin. Radiotherapy plus cisplatin is the standard of care for eligible patients with HPV-positive oropharyngeal carcinoma. Funding National Cancer Institute USA, Eli Lilly, and The Oral Cancer Foundation.

Purpose HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) carries a favorable prognosis for patients, yet nearly 30% of patients will experience disease relapse. We sought to detail patterns of failure, associated salvage therapy, and outcomes for patients with recurrent HPV-positive OPSCC. Methods and materials This is a single institution retrospective study of patients with recurrent HPV-positive OPSCC irradiated from 2002 to 2014. The primary study outcome was overall survival (OS, calculated using the Kaplan-Meier method). Secondary aims included patterns of first failure with descriptive details of salvage therapy. Solitary recurrences were defined as initial presentation of recurrence in a single site (primary, neck or oligometastatic), and multi-site was defined as local and regional and/or multiple sites of distant recurrence. Survival outcomes were compared using the log-rank test. Results The cohort consisted of 132 patients. The median follow-up was 59 months for surviving patients. Estimated 2-year and 5-year OS rates were 47% and 32%, respectively. Comparative 2-year and 5-year OS rates were 65% and 46% versus 19% and 9% for the solitary group and multi-site group, respectively (p Conclusions Patients with recurrent HPV-positive OPSCC experience 5-year survival of approximately 32%. However, patients with a “solitary” recurrence including disease at the primary site, neck or oligometastatic site have more favorable long-term outcomes.

Purpose Reirradiation of head and neck (H&N) cancer is a clinical challenge. Proton radiation therapy (PRT) offers dosimetric advantages for normal tissue sparing and may benefit previously irradiated patients. Here, we report our initial experience with the use of PRT for H&N reirradiation, with focus on clinical outcomes and toxicity. Methods and Materials We retrospectively reviewed the records of patients who received H&N reirradiation with PRT from April 2011 through June 2015. Patients reirradiated with palliative intent or without prior documentation of H&N radiation therapy were excluded. Radiation-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events Version 4.0. Results The conditions of 60 patients were evaluated, with a median follow-up time of 13.6 months. Fifteen patients (25%) received passive scatter proton therapy (PSPT), and 45 (75%) received intensity modulated proton therapy (IMPT). Thirty-five patients (58%) received upfront surgery, and 44 (73%) received concurrent chemotherapy. The 1-year rates of locoregional failure–free survival, overall survival, progression-free survival, and distant metastasis–free survival were 68.4%, 83.8%, 60.1%, and 74.9%, respectively. Eighteen patients (30%) experienced acute grade 3 (G3) toxicity, and 13 (22%) required a feeding tube at the end of PRT. The 1-year rates of late G3 toxicity and feeding tube independence were 16.7% and 2.0%, respectively. Three patients may have died of reirradiation-related effects (1 acute and 2 late). Conclusions Proton beam therapy can be a safe and effective curative reirradiation strategy, with acceptable rates of toxicity and durable disease control.

Background The purpose of this study was to evaluate the long-term outcomes after initial definitive or adjuvant radiotherapy (RT) for T3 laryngeal cancers. Methods We reviewed 412 patients treated for T3 laryngeal squamous cell cancer from 1985 to 2011. Results The 10-year overall survival (OS) was 35%; disease-specific-survival (DSS) was 61%; locoregional control was 76%; and freedom from distant metastasis was 83%. Chemotherapy, age, performance status

Cancer-associated facial pain can be caused by a variety of pathologic conditions. Here the authors describe the symptoms and incidence of facial pain secondary to three separate anatomic subcategories of cancer. The authors subsequently discuss the effectiveness and drawbacks of the most common methods of treatment.

We hypothesized that patients with oropharyngeal cancer treated with intensity modulated proton therapy (IMPT) would have lower symptom burdens, as measured by patient-reported outcome (PRO) surveys, than patients treated with intensity modulated photon therapy (IMRT).Patients were treated for oropharyngeal cancer from 2006 to 2015 through prospective registries with concurrent chemotherapy and IMPT or chemotherapy and IMRT and completed the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) module at various times before treatment (baseline), during treatment (acute phase), within the first 3 months after treatment (subacute phase), and afterward (chronic phase). Individual symptoms and the top 5 and top 11 most severe symptoms were summarized and compared between the radiation therapy modalities.PRO data were collected and analyzed from 35 patients treated with chemotherapy and IMPT and from 46 treated with chemotherapy and IMRT. The baseline symptom burdens were similar between both groups. The overall top 5 symptoms were food taste problems (mean score 4.91 on a 0-10 scale), dry mouth (4.49), swallowing/chewing difficulties (4.26), lack of appetite (4.08), and fatigue (4.00). Among the top 11 symptoms, changes in taste and appetite during the subacute and chronic phases favored IMPT (all P.048). No differences in symptom burden were detected between modalities during the acute and chronic phases by top-11 symptom scoring. During the subacute phase, the mean (±standard deviation) top 5 MDASI scores were 5.15 ± 2.66 for IMPT versus 6.58 ± 1.98 for IMRT (P=.013).According to the MDASI-HN, symptom burden was lower among the IMPT patients than among the IMRT patients during the subacute recovery phase after treatment. A prospective randomized clinical trial is underway to define the value of IMPT for the management of head and neck tumors.

Purpose To review our 15-year institutional experience using intensity modulated radiation therapy (IMRT) to reirradiate patients with head and neck squamous cell carcinomas (HNSCC) and identify predictors of outcomes and toxicity. Methods and Materials We retrospectively reviewed the records of 227 patients who received head and neck reirradiation using IMRT from 1999 to 2014. Patients treated with noncurative intent were excluded. Radiation-related acute and late toxicities were recorded. Prognostic variables included performance status, disease site, disease-free interval, chemotherapy, and RT dose and volume. Correlative analyses were performed separately for surgery and nonsurgery patients. Results Two hundred six patients (91%) were retreated with curative intent, and 173 had HNSCC histology; 104 (50%) underwent salvage resection, and 135 (66%) received chemotherapy. Median follow-up after reirradiation was 24.7 months. Clinical outcomes were worse for HNSCC patients, with 5-year locoregional control, progression-free survival, and overall survival rates of 53%, 22%, and 32%, respectively, compared with 74%, 59%, and 79%, respectively, for non-HNSCC patients. On multivariate analysis, concurrent chemotherapy and retreatment site were associated with tumor control, whereas performance status was associated with survival. Favorable prognostic factors specific to surgery patients were neck retreatment and lack of extracapsular extension, whereas for nonsurgery patients, these were a nasopharynx subsite and complete response to induction chemotherapy. Actuarial rates of grade ≥3 toxicity were 32% at 2 years and 48% at 5 years, with dysphagia or odynophagia being most common. Increased grade ≥3 toxicity was associated with retreatment volume >50 cm 3 and concurrent chemotherapy. Conclusions Reirradiation with IMRT either definitively or after salvage surgery can produce promising local control and survival in selected patients with head and neck cancers. Treatment-related toxicity remains significant. Prognostic factors are emerging to guide multidisciplinary treatment approaches and clinical trial design.

The purpose of this study was to investigate the setup and positioning uncertainty of a custom cushion/mask/bite‐block (CMB) immobilization system and determine PTV margin for image‐guided head and neck stereotactic ablative radiotherapy (HN‐SABR). We analyzed 105 treatment sessions among 21 patients treated with HN‐SABR for recurrent head and neck cancers using a custom CMB immobilization system. Initial patient setup was performed using the ExacTrac infrared (IR) tracking system and initial setup errors were based on comparison of ExacTrac IR tracking system to corrected online ExacTrac X‐rays images registered to treatment plans. Residual setup errors were determined using repeat verification X‐ray. The online ExacTrac corrections were compared to cone‐beam CT (CBCT) before treatment to assess agreement. Intrafractional positioning errors were determined using prebeam X‐rays. The systematic and random errors were analyzed. The initial translational setup errors were −0.8±1.3 mm, −0.8±1.6 mm, and 0.3±1.9 mm in AP, CC, and LR directions, respectively, with a three‐dimensional (3D) vector of 2.7±1.4 mm. The initial rotational errors were up to 2.4° if 6D couch is not available. CBCT agreed with ExacTrac X‐ray images to within 2 mm and 2.5°. The intrafractional uncertainties were 0.1±0.6 mm, 0.1±0.6 mm, and 0.2±0.5 mm in AP, CC, and LR directions, respectively, and 0.0∘±0.5°, 0.0∘±0.6°, and −0.1∘±0.4∘ in yaw, roll, and pitch direction, respectively. The translational vector was 0.9±0.6 mm. The calculated PTV margins mPTV(90,95) were within 1.6 mm when using image guidance for online setup correction. The use of image guidance for online setup correction, in combination with our customized CMB device, highly restricted target motion during treatments and provided robust immobilization to ensure minimum dose of 95% to target volume with 2.0 mm PTV margin for HN‐SABR. PACS number(s): 87.55.ne

Purpose A single-institution prospective study was conducted to assess disease control and toxicity of proton therapy for patients with head and neck cancer. Methods and materials Disease control, toxicity, functional outcomes, and patterns of failure for the initial cohort of patients with oropharyngeal squamous carcinoma (OPC) treated with intensity modulated proton therapy (IMPT) were prospectively collected in 2 registry studies at a single institution. Locoregional failures were analyzed by using deformable image registration. Results Fifty patients with OPC treated from March 3, 2011, to July 2014 formed the cohort. Eighty-four percent were male, 50% had never smoked, 98% had stage III/IV disease, 64% received concurrent therapy, and 35% received induction chemotherapy. Forty-four of 45 tumors (98%) tested for p16 were positive. All patients received IMPT (multifield optimization to n=46; single-field optimization to n=4). No Common Terminology Criteria for Adverse Events grade 4 or 5 toxicities were observed. The most common grade 3 toxicities were acute mucositis in 58% of patients and late dysphagia in 12%. Eleven patients had a gastrostomy (feeding) tube placed during therapy, but none had a feeding tube at last follow-up. At a median follow-up time of 29 months, 5 patients had disease recurrence: local in 1, local and regional in 1, regional in 2, and distant in 1. The 2-year actuarial overall and progression-free survival rates were 94.5% and 88.6%. Conclusions The oncologic, toxicity, and functional outcomes after IMPT for OPC are encouraging and provide the basis for ongoing and future clinical studies.

PURPOSE: Postoperative radiation is often indicated in the treatment of malignant epithelial tumors of the orbit and ocular adnexa. We present details of radiation technique and toxicity data after orbit-sparing surgery followed by adjuvant proton radiation therapy. METHODS AND MATERIALS: Twenty patients underwent orbit-sparing surgery followed by proton therapy for newly diagnosed malignant epithelial tumors of the lacrimal gland (n=7), lacrimal sac/nasolacrimal duct (n=10), or eyelid (n=3). Tumor characteristics, treatment details, and visual outcomes were obtained from medical records. Acute and chronic toxicity were prospectively scored using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median radiation dose was 60 Gy(RBE) (relative biological effectiveness; [range 50–70 Gy]); 11 patients received concurrent chemotherapy. Dose to ipsilateral anterior optic structures was reduced in 13 patients by having them gaze away from the target during treatment. At a median follow-up time of 27.1 months (range 2.6–77.2 months), no patient had experienced local recurrence; 1 had regional and 1 had distant recurrence. Three patients developed chronic grade 3 epiphora, and 3 developed grade 3 exposure keratopathy. Four patients experienced a decrease in visual acuity from baseline but maintained vision sufficient to perform all activities of daily living without difficulty. Patients with grade ≥3 chronic ocular toxicity had higher maximum dose to the ipsilateral cornea (median 46.3 Gy[RBE], range 36.6–52.7 Gy[RBE] vs median 37.4 Gy[RBE], range 9.0–47.3 Gy(RBE); P=.017). CONCLUSIONS: Orbit-sparing surgery for epithelial tumors of the orbit and ocular adnexa followed by proton therapy successfully achieved disease control and was well tolerated. No patient required orbital exenteration or enucleation. Chronic grade 3 toxicity was associated with high maximum dose to the cornea. An eye-deviation technique can be used to limit the maximum corneal dose to

BACKGROUND Favorable outcomes for human papillomavirus–associated oropharyngeal cancer have led to interest in identifying a subgroup of patients with the lowest risk of disease recurrence after therapy. De-intensification of therapy for this group may result in survival outcomes that are similar to those associated with current therapy but with less toxicity. To advance this effort, this study analyzed the outcomes of oropharyngeal cancer patients treated with or without systemic therapy. METHODS This was a retrospective study of patients with oropharyngeal cancer treated between 1985 and 2012. The criteria for inclusion were ≤10 pack-years of cigarette smoking and stage III/IVA cancer limited to T1-3, N1-N2b, and T3N0 disease. A survival analysis was performed with the primary endpoint of progression-free survival (PFS). RESULTS The cohort included 857 patients. Systemic therapy was given to 439 patients (51%). The median survival was 80 months. The 2-year PFS rate was 91%. When the analysis was limited to 324 patients irradiated without systemic therapy, the 2- and 5-year PFS rates were 90% and 85%, respectively. Furthermore, for these 324 patients, the 5-year PFS rates for T1, T2, and T3 disease were 90%, 83%, and 70%, respectively. The 5-year PFS rate for patients treated with systemic therapy for T3 disease was 77% (P = .07). CONCLUSIONS According to the low-risk definition currently established in cooperative trials, the patients had a 2-year PFS rate approximating 90%. When patients who were treated with radiation alone were evaluated, no compromise was observed in this high rate of PFS, which is higher than the 2-year PFS thresholds used in current cooperative trials. Cancer 2016. © 2016 American Cancer Society.

Background This study assessed outcomes of patients with hypopharyngeal carcinoma treated with organ-preservation therapy utilizing intensity-modulated radiation therapy (IMRT). Methods The medical records of 98 patients treated with definitive IMRT +/- chemotherapy from 2001 to 2013 for nonmetastatic hypopharyngeal cancer were retrospectively reviewed. Results Patients were treated to doses of 66 to 72 Gy. Eighty-three patients (85%) received chemotherapy. With median follow-up of 35 months, 2-year overall survival (OS), locoregional control, progression-free survival (PFS), and laryngectomy-free survival rates were 74%, 77%, 67%, and 65%, respectively. Functional laryngeal preservation rate was 76% at 2 years. N3 disease correlated with worse OS (p < .01). Concurrent chemotherapy correlated with improved locoregional control (p = .03) and complete response to induction chemotherapy correlated with improved OS and PFS (p = .02). Actuarial 2-year and 5-year grade 3 treatment toxicities were 17% and 21%, respectively. Conclusion Favorable disease outcomes and functional laryngeal preservation rates can be achieved with IMRT for patients with hypopharyngeal cancer. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Background The purpose of this study was to present our evaluation of the clinical and functional outcomes after salvage total laryngectomy (STL). Methods We conducted a retrospective review of 218 patients who underwent STL between 1994 and 2014. Results Seventy percent of patients originally had T1 or T2, N0 tumors and 73% had definitive external-beam radiotherapy (EBRT) alone. A majority utilized tracheoesophageal prosthesis (77%) and were gastrostomy free (80%) at last follow-up. The 5-year disease control and overall survival (OS) rates were 65% and 57%, respectively. Patients with a disease-free interval after initial treatment 5-year disease-free interval and 60% for

Background This was a retrospective study of patients with human papillomavirus (HPV)-associated oropharyngeal cancer treated with concurrent systemic therapy and radiation. Methods Data were extracted through chart review, and statistical analyses included frequency tabulation, chi-square, and Kaplan–Meier tests. Results Three hundred thirty-nine patients were analyzed; 166 received neoadjuvant chemotherapy. One hundred thirty-six patients were treated with cisplatin, 123 with cetuximab, and 59 with carboplatin. The 2-, 3-, and 5-year actuarial overall survival rates were 92%, 88%, and 78%, respectively. There were no significant differences in survival or disease control when analyzed by systemic agent. Platin-treated patients had greater hematologic toxicity, and required more intravenous hydration. The incidence of confluent mucositis was highest among patients treated with cetuximab. Conclusion Platin and cetuximab seem to have similar efficacy when delivered concurrently with radiation in our retrospective population study. Although platin did cause greater hematologic toxicity, radiation-specific side effects seemed relatively comparable. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Background Overexpression of p16 is associated with improved outcomes among patients with oropharyngeal carcinoma. However, its role in the outcomes of patients with nasopharyngeal cancer (NPC) remains unclear. Methods Eighty-six patients with NPC treated at MD Anderson Cancer Center from 2000 to 2014 were identified. Epstein-Barr virus (EBV) and human papillomavirus (HPV) status were determined by in situ hybridization (ISH) and p16 by immunohistochemical staining. Results EBV positivity was associated with extended overall survival (OS; median, 95.0 vs 44.9 months; p < .004), progression-free survival (PFS; median, 80.4 vs 28.1 months; p < .013), and locoregional control (median, 104.4 vs 65.5 months; p < .043). In patients with EBV-positive tumors, p16 overexpression correlated with improved PFS (median, 106.3 vs 27.1 months; p < .02) and locoregional control (median, 93.6 vs 64.5 months; p < .02). Conclusion P16 overexpression is associated with improved PFS and locoregional control in patients with EBV-positive NPC. P16 expression may complement EBV status in predicting treatment outcomes for patients with NPC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1459–E1466, 2016

The purpose of this study is to evaluate potential associations between increased platelets and oncologic outcomes in oropharyngeal cancer patients receiving concurrent chemoradiation. A total of 433 oropharyngeal cancer patients (OPC) treated with intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy between 2002 and 2012 were included under an approved IRB protocol. Complete blood count (CBC) data were extracted. Platelet and hemoglobin from the last phlebotomy (PLTpre-chemoRT, Hgbpre-chemoRT ) before start of treatment were identified. Patients were risk-stratified using Dahlstrom-Sturgis criteria and were tested for association with survival and disease-control outcomes. Locoregional control (LRC), freedom from distant metastasis (FDM) and overall survival (OS) were decreased (p

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.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.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 (p0.05 for each), but absolute differences were small. Overall, 51% had no more than mild symptom ratings across all 22 symptoms assessed.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.

Background and purpose Customized mouth-opening-tongue-depressing-stents (MOTDs) may reduce toxicity in patients with head and neck cancers (HNC) receiving radiotherapy (RT). However, making MOTDs requires substantial resources, which limits their utilization. Previously, we described a workflow for fabricating customized 3D-printed MOTDs. This study reports the results of a prospective trial testing the non-inferiority of 3D-printed to standard and commercially-available (TruGuard) MOTDs as measured by patient reported outcomes (PROs). Materials and methods PROs were collected at 3 time points: (t1) simulation, (t2) prior to RT, (t3) between fractions 15–25 of RT. Study participants received a 3D-printed MOTDs (t1, t2, t3), a wax-pattern (t1), an acrylic-MOTDs (t2, t3) and an optional TruGuard (t1, t2, t3). Patients inserted the stents for 5–10 min and completed a PRO-questionnaire covering ease-of-insertion and removal, gagging, jaw-pain, roughness and stability. Inter-incisal opening and tongue-displacement were recorded. With 39 patients, we estimated 90% power to detect a non-inferiority margin of 2 at a significance level of 0.025. Matched pairs and t-test were used for statistics. Results 41 patients were evaluable. The 3D-printed MOTDs achieved a significantly better overall PRO score compared to the wax-stent (p = 0.0007) and standard-stent (p = 0.0002), but was not significantly different from the TruGuard (p = 0.41). There was no difference between 3D-printed and standard MOTDs in terms of inter-incisal opening (p = 0.4) and position reproducibility (p = 0.98). The average 3D-printed MOTDs turn-around time was 8 vs 48 h for the standard-stent. Conclusions 3D-printed stents demonstrated non-inferior PROs compared to TruGuard and standard-stents. Our 3D-printing process may expand utilization of MOTDs.

Background: Patients with HPV-related oropharynx cancer have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with cetuximab can preserve high survival and reduce toxicity is unknown. We performed a randomized trial comparing survival and toxicity in 987 patients enrolled at 182 health care centers in the US and Canada between July 2011 and July 2014. Methods: Eligibility included histologically confirmed HPV positive carcinoma, clinical stage TI-T2, N2-N3 or T3-T4, N0-N3. Zubrod status 0 or 1. All patients received intensity modulated radiotherapy (IMRT) delivered in 35 fractions to 70 gray over 6 weeks using 6 fractions per week. High-dose cisplatin at 100 mg/m² was given every 3 weeks for 2 cycles in arm A (standard of care) versus arm B loading dose cetuximab plus weekly cetuximab. Patients were stratified by T category, N category, Zubord performance status, and smoking history. Primary analysis was based on modified intention to treat for all patients meeting eligibility criteria. 849 patients were randomly assigned to radiation plus cetuximab (425) or radiotherapy plus cisplatin (424). Median follow-up is 4.5 years. Results: Radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival. Estimated 5-year overall survival was 78% in the cetuximab group versus 85% in the cisplatin group (p=0.016). Progression-free survival was 67% versus 78% (p=0.0002). Local-regional failure was higher in the cetuximab group, 17% versus 10% (p=0.005). High-grade acute toxicity was similar at 77% for both groups. Late toxicity was also similar. Conclusions: For HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab showed inferior overall survival, progression-free survival, and locoregional control compared with radiation plus cisplatin. This study defines radiation using IMRT plus cisplatin as the standard of care for this population. *Lancet. Vol 393, p 40-50, January 5, 2019 Citation Format: J.A. Ridge, J. Ringash, M. Yao, D.M. Blakaj, M.A. Razaq, A.D. Colevas, J.J. Beitler, C.U. Jones, N.E. Dunlap, S.A. Seaward, S. Spencer, T.J. Galloway, J.J. Dignam, Q.T. Le, M.L. Gillison, E.M. Sturgis, J. Phan, A.M. Trotti, J. Harris, A. Eisbruch, P.M. Harari, D.J. Adelstein, S.A. Koyfman, B. Burtness. Radiotherapy plus cetuximab or cisplatin in human papilloma-virus positive oropharyngeal cancer (NRG 1016): A randomized multicenter noninferiority trial [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr IA20.

Objectives Prior reports have demonstrated a potential enhancement in overall response rate (ORR) to chemotherapy after exposure to immunotherapy. The goal of this study was to evaluate the ORR and survival to chemotherapy and/or targeted therapy in head and neck squamous cell carcinoma (HNSCC) patients who progressed on immune checkpoint inhibitors (ICI). Materials and Methods We retrospectively collected clinical and pathologic data from patients with recurrent/metastatic HNSCC who progressed on ICI and subsequently received chemotherapy or targeted therapy. ORR was assessed by RECIST version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results A total of 43 patients met criteria for inclusion. The majority were male (91%) and former smokers (60%). Most patients received ICI as first-line (58.14%); the vast majority was platinum exposed (90.7%). The ORR to ICI was 21%. The ORR to systemic therapy before ICI was 47%, and the ORR after ICI failure was 42%. After progression on ICI, the median PFS and OS on the subsequent line of therapy were 4.2 and 8.4 months respectively. Conclusion In our cohort of recurrent/metastatic HNSCC patients, the ORR and OS to systemic therapy after progression on ICI were higher than historical controls for second-line or beyond. Further investigations are warranted to better characterize optimal sequencing and combination strategies.

Magnetic resonance imaging (MRI) has improved capacity to visualize tumor and soft tissue involvement in head and neck cancers. Using advanced MRI, we can interrogate cell density using diffusion weighted imaging, a quantitative imaging that can be used during radiotherapy, when diffuse inflammatory reaction precludes PET imaging, and can assist with target delineation as well. Correlation of circulating tumor cells (CTCs) measurements with 3D quantitative tumor characterization could potentially allow selective, patient-specific response-adapted escalation or de-escalation of local therapy, and improve the therapeutic ratio, curing the greatest number of patients with the least toxicity. The proposed study is designed as a prospective observational study and will collect pretreatment CT, MRI and PET/CT images, weekly serial MR imaging during RT and post treatment CT, MRI and PET/CT images. In addition, blood sample will be collected for biomarker analysis at those time intervals. CTC assessments will be performed on the CellSave tube using the FDA-approved CellSearch® Circulating Tumor Cell Kit (Janssen Diagnostics), and plasma from the EDTA blood samples will be collected, labeled with a de-identifying number, and stored at − 80 °C for future analyses. The primary objective of the study is to evaluate the prognostic value and correlation of weekly tumor response kinetics (gross tumor volume and MR signal changes) and circulating tumor cells of mucosal head and neck cancers during radiation therapy using MRI in predicting treatment response and clinical outcomes. This study will provide landmark information as to the utility of CTCs (‘liquid biopsy) and tumor-specific functional quantitative imaging changes during treatment to guide personalization of treatment for future patients. Combining the biological information from CTCs and the structural information from MRI may provide more information than either modality alone. In addition, this study could potentially allow us to determine the optimal time to obtain MR imaging and/ or CTCs during radiotherapy to assess tumor response and provide guidance for patient selection and stratification for future dose escalation or de-escalation strategies. Clinicaltrials.gov ( NCT03491176 ). Date of registration: 9th April 2018. (retrospectively registered). Date of enrolment of the first participant: 30th May 2017.

OBJECTIVES We aim to report oncologic outcomes after conventional radiotherapy (ConRT) using opposed lateral beams and intensity-modulated radiation therapy (IMRT) for tumor (T)1 nodal (N)0 T1 N0 glottic squamous cell carcinoma. STUDY DESIGN Retrospective case-control study. METHODS We retrospectively reviewed demographic, disease, and treatment characteristics for patients treated at our institution during 2000 to 2013. RESULTS One hundred fifty-three patients (71%) were treated using ConRT and 62 (29%) using IMRT. The median follow-up for all patients was 68 months. There was no statistically significant difference in 5-year local control between patients with T1a versus T1b disease (94% vs. 89%, respectively, P = 0.5). Three-year locoregional control for patients treated with ConRT was 94% compared to 97% with IMRT (P = 0.4). Three-year overall survival (OS) for patients treated with ConRT was 92.5% compared with 100% with IMRT (P = 0.1). Twelve of 14 patients with local recurrence underwent salvage surgery with 5-year ultimate locoregional control of 98.5% and 97.1% in the ConRT and IMRT cohorts, respectively (P = 0.7). Multivariate analysis showed age

Treatment of Nasopharyngeal Carcinoma (NPC) has been based on the Intergroup 0999 trial with chemoradiation (CRT) and consolidation chemotherapy (CT). While effective, toxicities are significant. As a result, many oncologists use induction chemotherapy (IC) followed by CRT, citing better tolerance with anecdotally no worse outcome. We reviewed 95 NPC patients treated between 2005 and 2015 at MDACC with IC followed by CRT. Median age was 49 years. Fifty-seven were T3/T4 and 62 were N2-3. The most common IC regimen was a platinum-taxane doublet (N = 72). 83 patients completed IC. Grade 3–4 toxicities with IC occurred in 10 patients. There were 15 primary site complete responses (CR), 68 partial responses (PR),6 stable disease (SD), and 2 progressed. There were 10 nodal CR, 73 PR, 4 SD, and 3 progressed. 92 patients received RT, 74 with CRT. At completion of treatment, there were 81 CR and 8 PR patients. Post radiation toxicities included mucositis and skin rash (37), oto- toxicity (25), PEG placement (12), and osteonecrosis (2). Three-year progression free survival (PFS) and distant metastasis free survival (DMFS) were 77.3% and 78%. CRT for advanced NPC is standard, but IC remains controversial. Early trials failed to show a benefit but used older chemotherapy and pre-intensity modulated radiation therapy (IMRT) methods. Modern trials with platinum-taxane regimens and IMRT have shown reasonable PFS and OS results with acceptable toxicity. This retrospective review of IC followed by CRT showed acceptable toxicity and good response and survival outcomes. This approach has, for many oncologists, become a standard.

Skull base reirradiation is challenging due to complex anatomy, enrichment of treatment-resistant clonogens, and increased risk of severe treatment complications. Without local therapy, early mortality is certain and tumor progression can result in debilitating symptoms. Modern radiotherapy advancements, such as image-guided radiation therapy (IGRT), intensity-modulated radiation therapy (IMRT), particle therapy, and stereotactic radiation therapy (SRT), are attractive for skull base reirradiation. Although limited by their retrospective nature and heterogeneous patient populations, several studies have demonstrated that reirradiation with these highly conformal techniques is feasible. Compared to IMRT or particle therapy reirradiation, SRT reirradiation appears promising with lower toxicity and increased convenience. Here, we provide thorough explanations for each technology and summarize the most relevant and recent studies, with particular attention to efficacy and toxicity. Skull base reirradiation using these extremely conformal therapy techniques requires meticulous treatment planning and should be delivered by experienced teams.