Recurrent Head And Neck Cancer Research Articles

A qualitative examination of patient priorities and preferences during treatment decision-making for recurrent head and neck cancer.

Patients with recurrent head and neck cancer (HNC) may feel overwhelmed at the prospect of having to consider treatment options particularly if they recently completed treatment for their primary disease or when they have no options that may lead to long-term survival. The purpose of this study was to examine patient priorities and preferences during treatment decision-making for recurrent HNC. Individuals with newly diagnosed recurrent HNC were recruited at a National Cancer Institute-Designated Cancer Center. Participants were interviewed using a structured interview guide. Descriptive statistics were used to describe participants, and qualitative template analysis was used to analyze interview data. Participants (n = 38) considered information from healthcare providers, likelihood of treatment success, and other patient-specific factors in making their treatment decisions. Although patients with recurrent HNC endorse a myriad of decision-making factors, the recommendation of their healthcare provider and the likelihood of treatment success are of paramount importance. Future research should focus on methods to rapidly identify patient priorities at the time of diagnosed recurrence while respecting patient coping and communication styles.

Comparison of tumor delineation using dual energy computed tomography versus magnetic resonance imaging in head and neck cancer re-irradiation cases.

In treatment planning, multiple imaging modalities can be employed to improve the accuracy of tumor delineation but this can be costly. This study aimed to compare the interobserver consistency of using dual energy computed tomography (DECT) versus magnetic resonance imaging (MRI) for delineating tumors in the head and neck cancer (HNC) re-irradiation scenario. Twenty-three patients with recurrent HNC and had planning DECT and MRI were identified. Contoured tumor volumes by seven radiation oncologists were compared. Overall, T1c MRI performed the best with median DSC of 0.58 (0-0.91) for T1c.T1c MRI provided higher interobserver agreement for skull base sites and 60kV DECT provided higher interobserver agreement for non-skull base sites.

Pembrolizumab treatment increases chemotaxis of cytotoxic T cells in head and neck cancer patients within the adenosine‐rich tumor microenvironment

Head and neck cancer (HNC) is the sixth most common cancer worldwide with a five‐year survival rate of 50%. Immunotherapy has been emerging as a promising treatment modality as conventional treatment strategies (surgery, chemotherapy and radiation) have limited efficacy and cause debilitating co‐morbidities. Immunotherapy harnesses the patient’s own immune system to fight disease. Targeting the immune system is crucial because immune cell (specifically cytotoxic T cell) infiltration into the tumor microenvironment (TME) and subsequent cytotoxicity is critical for tumor elimination. Pembrolizumab, an anti‐PD‐1 (programmed cell death‐1 receptor) antibody, is an immunotherapy currently approved for metastatic or recurrent unresectable HNC and is in clinical trials for curative intent. While there have been promising long‐lasting clinical responses to Pembrolizumab, many patients still do not respond. Thus, it is critical to understand the mechanism of action of Pembrolizumab in order to reduce treatment resistance. Moreover, it has been shown that Pembrolizumab increases cytotoxic T cell density in the TME; nevertheless, the underlying mechanism is not fully understood. However, it is known that there is an increased accumulation of adenosine (Ado), an anti‐inflammatory purine nucleoside, in the TME of HNC patients, which inhibits T cell chemotaxis by blocking the function of the potassium ion channel, KCa3.1. Therefore, to elucidate possible effects of Pembrolizumab on T cell chemotaxis, we studied KCa3.1 activity and subsequent chemotaxis in CD8+ peripheral blood T cells (PBTs) of naïve (never treated) HNC patients before/after Pembrolizumab treatment (n=25) via electrophysiological and 3D chemotaxis experiments. Furthermore, Pembrolizumab treated patients were categorized as responders (R) or non‐responders (NR) based on treatment response (i.e., reduction in tumor viability with a cutoff of ≥20% for R). We observed that Pembrolizumab increased the KCa3.1 activity in post‐treatment patient PBTs by 29.8% (p=0.026). Because we observed an increase in KCa3.1 activity in treated patients, we next assessed whether there was an effect on the chemotaxis of PBTs in presence of Ado. While Ado inhibited the chemotactic ability in treatment naïve PBTs by 53.9% (p<0.001, n=22), we determined that post‐treatment R PBTs were not inhibited by Ado (p = 0.142, n=11) whereas post‐treatment NR PBTs were inhibited by Ado (p = 0.005, n=10). These data support a role of ion channels and chemotaxis in patient response to Pembrolizumab and could lead to better understanding of the effect of Pembrolizumab in immune cell infiltration into the tumor and, ultimately, its mechanism of action/resistance.Support or Funding InformationDoD CA160714; T32CA117846; 2R01 CA95286

Stereotactic body radiotherapy for medically unfit patients with cancers to the head and neck.

A single institutional experience of stereotactic body radiation therapy (SBRT) to medically unfit patients with unresectable head and neck cancers (HNCs). A retrospective review of HNC patients undergoing SBRT was undertaken from 2011 to 2016 for fractionation ranges between 35 and 50 Gy in 4 to 6 fractions. One hundred and fourteen patients with 117 SBRT courses were included with mean follow-up of 10.5 months. The cohort consisted of previously untreated primary HNC (n = 48), recurrent never irradiated HNC (n = 19), oligometastatic (n = 17) non-HNC primaries and previously irradiated HNC (n = 33). Local control (LC) at 12 months and median progression free survival was 85.8%, 78.2%, 85%, 78.9% (P = .86) and 23.7, 14.8, 10.5 and 7.8 months (P = .04) respectively. Only one patient had an acute grade 4 toxicity, two patients had grade 4 late toxicities. HNC SBRT is an effective treatment for frail patients where longer LC is relevant but are unable to tolerate protracted radiation schedules.

Stereotactic ablative radiotherapy (SABR) for recurrent and previously irradiated head and neck cancers.

Objective:To assess the response and toxicity of stereotactic ablative radiotherapy (SABR) in patients with recurrent head and neck cancer (HNC), who had previously received radiation for their primary tumor.Methods:Between 2014 and 2018, patients who received SABR to recurrent HNC within the previously irradiated region were retrospectively reviewed. Mean age was 60 years (range 30–78 Years). Histology was confirmed in all patients. MRI and /or CT-positron emission tomography were done to evaluate local extent and to rule out metastasis. Response was assessed as per RECIST/PERCIST Criteria. Cox proportional hazards regression and the Kaplan–Meier methods were used for statistical analysis.Results:32 patients received SABR. RPA Class II, III patients were 20 and 12 respectively. 87% patients received a dose of ≥30 Gy/5 fractions. Median follow-up was 12 months. Estimated 1 year and 2 years local control was 64.2 and 32% and 1 year and 2 years overall survival was 67.5 and 39.5% respectively. Acute Grade 2 skin and Grade 3 mucosal toxicity was seen in 31.3 and 28% patients respectively. Late Grade 3 toxicity was seen in 9.3% patients.Conclusion:Re-irradiation with SABR yields high local control rates and is well tolerated. It compares favorably with other treatment modalities offered to patients with recurrent HNC. It is also suitable for patients of RPA Class II and III. There is need for novel systemic agents to further improve the survival.Advances in knowledge:Treatment of patients with recurrent HNC is challenging and is more difficult in previously radiated patient. More than 50% patients are unresectable. Other options of salvage treatment like re-irradiation and chemotherapy are associated with poor response rates and high incidence of acute and late toxicity (Gr ≥3 toxicity 50–70%). SABR is a novel technology to deliver high dose of radiation to recurrent tumor with high precision. It yields high local control rates with less toxicity compared to conventionally fractionated radiation.

Next generation sequencing of cell free circulating tumor DNA in blood samples of recurrent and metastatic head and neck cancer patients.

BackgroundEffective targeted therapy is lacking in head and neck cancer (HNC). The use of next generation sequencing (NGS) has been suggested as a way to potentially expand therapeutic options and improve outcomes. This study was performed in order to further characterize blood sample cell-free circulating tumor DNA (ctDNA) in advanced HNC patients, to determine its ability to identify actionable mutations, and to elucidate its potential role in patient management.MethodsRetrospective analysis of 60 patients with recurrent and metastatic (R/M) HNCs who underwent molecular profiling of blood samples utilizing Guardant360, a 70-gene ctDNA NGS platform. ctDNA sequencing data was compared to tumor NGS data, when available. Best response to therapy was assessed using RECIST measures.ResultsThe most common tumor type was oropharyngeal squamous cell carcinoma (n=21). Other cancer types included salivary gland (n=8) and thyroid (n=4). The most common mutations identified by blood analysis were TP53 (68% of patients), PIK3CA (34% of patients), NOTCH1 (20% of patients), and ARID1A (15% of patients). These findings were consistent with results from tumor sequencing data (n=30) where TP53 (48%) and PIK3CA (24%) were also the most common. Seventy-three percent (n=22) of patients had alterations identified in blood that were not present in tumor specimens. In patients with squamous cell carcinoma, 66% had an off-label option identified and 90% had a trial option identified, while 50% of patients with salivary primaries had off-label option identified and 75% had trial options identified. All patients (n=3, 100%) with thyroid primaries had off-label and clinical trial options identified. Of patients with actionable mutations, 13% (n=8) received matched targeted therapy (MTT). Three patients had stable disease (37.5%), 3 had progressive disease (37.5%), and 2 (25%) were not evaluated at the time of follow up. Of those who did not receive targeted therapy (n=21), 11 patients had stable disease (52.4%), 9 had progressive disease (42.9%), and 1 had a complete response (4.8%).ConclusionsAlterations identified by ctDNA may help inform management decisions in advanced HNC. The majority of patients had unique mutations identified on ctDNA. The role of NGS of ctDNA should be explored in future studies.

Brachytherapy in head and neck malignancies: Indian Brachytherapy Society (IBS) recommendations and guidelines.

PurposeBrachytherapy (BT) forms major treatment modality in squamous cell carcinoma of head and neck cancers (HNC). However, there is a dearth of literature and guidelines for the use in various indications. High-dose-rate brachytherapy (HDR-BT) in Indian scenario is an important treatment modality, and the recommendations in this guidelines aim to provide the necessary recommendations for the use of HDR-BT for uniform application across the country in patients with HNC.Material and methodsA panel consisting of members of the Indian Brachytherapy Society (IBS), based on their clinical experience was invited. The process involved defining important steps, precautions, target volumes and indications, thorough literature review, and discussion with fellow members. The guidelines were established and formulated the recommendations for HDR-BT based on available evidences and individual experience for sites, relevant to Indian settings.ResultsThe IBS recommends the use of HDR brachytherapy as a part of treatment of head and neck tumors. The scope of these guidelines and recommendations included practical suggestions, ensuring efficient use of brachytherapy treatment as radical with external beam radiotherapy (EBRT) boost, palliative and adjuvant as definitive, or re-radiation as salvage for HNC in India. The IBS has made specific site-wise recommendations for previously untreated and recurrent HNC patients on their selection criteria, implant techniques, target volume definition, and HDR treatment parameters, such as time, dose rate, total dose, and fractionation schedules. Limited experience exists with HDR-BT in patients with head and neck cancers in India and across the globe.ConclusionsIBS provided a consensus statement and guidelines for the head and neck brachytherapy and believed that these recommendations will overcome the fear of practicing radiation oncologists. This should generate interest amongst students and will help radiation oncologists all across the country to use the art of brachytherapy carefully in HNC patients, with better curative and salvage options.

Dose-Limiting Organs at Risk in Carbon Ion Re-Irradiation of Head and Neck Malignancies: An Individual Risk-Benefit Tradeoff.

Background: Carbon ion re-irradiation (CIR) was evaluated to investigate treatment planning and the consequences of individual risk-benefit evaluations concerning dose-limiting organs at risk (OAR). Methods: A total of 115 consecutive patients with recurrent head and neck cancer (HNC) were analyzed after initial radiotherapy and CIR at the same anatomical site. Toxicities were evaluated in line with the Common Terminology Criteria for Adverse Events 4.03. Results: The median maximum cumulative equivalent doses applied in fractions of 2 Gy (EQD2) to the brainstem, optic chiasm, ipsilateral optic nerve, and spinal cord were 56.8 Gy (range 0.94–103.9), 51.4 Gy (range 0–120.3 Gy), 63.6 Gy (range 0–146.1 Gy), and 28.8 Gy (range 0.2–87.7 Gy). The median follow up after CIR was 24.0 months (range 2.5–72.0 months). The cumulative rates of acute and late severe (≥grade III) side effects after CIR were 1.8% and 14.3%. Conclusion: In recurrent HNC, an individual risk-benefit tradeoff is frequently inevitable due to unfavorable location of tumors in close proximity to vital OAR. There are uncertainties about the dose tolerance of OAR after CIR, which warrant increased awareness about the potential treatment toxicity and further studies on heavy ion re-irradiation.

Alterations in genetic pathways following radiotherapy for head and neck cancer.

Radiotherapy (RT) is an integral component in the treatment of head and neck cancer (HNC).We hypothesized there would be alterations in gene-expression and pathway activity in HNC samples obtained in recurrent HNC that were previously treated with RT, when compared to RT-naïve disease. Patient data was abstracted from a prospectively maintained database. Linear-microarray analysis and supervised gene-set enrichment-analysis were employed to compare RT-naive and recurrent disease after prior-RT. A total of 157 patients were analyzed, 96 (61%) were RT-naive and 61 (39%) had RT.After radiation, there was upregulation of genes associated with angiogenesis, protein-translation-machinery, cell-cycle regulation, and growth factors, and downregulation associated with Myc activity, and hypoxic response (all P < .001).Previously irradiated HNC was associated with downregulation in 19/42 genes in the Wnt/B-catenin-pathway (P = .045)and 119/199 genes involved in the MYC target pathway (P = .024). Patients with recurrences salvaged surgically post-RT had significant alterations in gene-expression and in Wnt/B-catenin and MYC-target pathways. These pathways may represent potential targets to prevent development of resistance to RT.

Clinical Outcomes after Re-irradiation in Recurrent Head and Neck Cancers treated with Intensity Modulated Proton and Photon Therapies

Loco-regional recurrence remains a challenge regardless of primary treatment modality in head and neck cancer (HNC). Re-irradiation (RR) is a potential option for local control in previously irradiated patients. We report our institutional experience comparing clinical outcomes in recurrent HNC treated curatively with intensity modulated proton (IMPT) and photon (IMRT) therapy. This is an IRB approved retrospective analysis of prospectively collected outcomes for loco-regionally recurrent or second primary HNC. All patients were treated with radiation to head and neck region at least once previously. Local recurrence (LR), overall survival (OS), disease-free survival (DFS) and acute toxicities occurring within 3 months of RR were analyzed. Statistical tools included Chi-square, Wilcoxon Rank Sum, Fischer Exact, and Unequal Variance T-Tests. We evaluated 44 patients with loco-regional recurrence treated with RR to the head and neck between April 2013 and December 2018. It included 26 patients (59%) treated with IMPT and 18 (41%) with IMRT. Median follow-up was 1.7 years in all patients with at least one year follow-up in both arms. All patients were treated with curative intent. Overall median RR dose was 63 Gy (IMPT=61.5 Gy, IMRT=69.6 Gy) whereas the overall median total dose was same in both arms, 130 Gy. IMPT used conventional fractionation in 17 (65%), SBRT in 8 (31%), and hyperfractionation in 1 (4%) patients. IMRT utilized hyperfractionation in 14 (78%), conventional in 3 (17%) and 1 (6%) SBRT. IMPT was found to have significantly lower rates of physician-reported overall grade 3 (G3) acute toxicities 31% vs 73% in IMRT (p=0.01). This included dysphagia (4% vs 39%, p=0.01), mucositis (8% vs 39%, p=0.001), and dermatitis (12% vs 33%, p=0.03). Commonly treated sites were 52% mucosal (n=23), 14% neck/nodal sites (n=6), and 32% both mucosal and neck sites (n=14), and 2% (n=1) cutaneous only treatment. IMPT patients with mucosal site RR had lower chances of G3 dysphagia (5% vs 40%, p=0.01) and lower G3 mucositis (9% vs 47%, p=0.02); and those with neck nodal/neck RR had lower chances of G3 dermatitis (18% vs 56%, p=0.16). OS at 2-year was 69% with IMPT compared to 58% with IMRT cohort (p=0.26). 2-year LR was 9.5% with IMPT vs 6.5% with IMRT (p=0.66). 2-year DFS was 54% with IMRT compared to 46% with IMPT, respectively (p=0.94). RR is a safe and effective treatment option in the management of recurrent HNC. IMPT RR was found to carry reduced rates of grade 3 toxicity compared to IMRT. IMPT appears to confer a similar rate of OS, DFS and LR compared to IMRT, although these results warrant further exploration in the form of larger prospective studies with longer follow up.

A Pilot Study Using Intraoperative Placement of Cesium-131 Permanent Interstitial Brachytherapy in Resectable High Risk Recurrent Head and Neck Cancer

To determine the feasibility and safety of Cesium-131 implant in the management of recurrent head and neck cancer (HNC). This is a prospective trial approved by institutional IRB. Eligibility includes patients with resectable, recurrent failures who had a prior history of radiation to the head and neck deemed high risk for a second failure by our multidisciplinary tumor board. The strength and numbers of the Cesium 131 seeds were estimated based on a preoperative treatment plan with diagnostic CT images. Immediately after tumor extirpation, the seeds were implanted in the surgical bed based on the preoperative treatment plan with intraoperative adjustment. The surgical bed and the seeds were covered with a regional flap or microvascular free flap. A CT of neck was obtained on postoperative day 1 to confirm the dose distribution of the implant. The patient followed up at 1 month and 3 months after surgery, then every 3 months in the first two years. PET/CT scans or CT neck and chest with contrast was obtained at 3 months and one year after surgery. From November 2016 to September 2018, 15 patients were recruited, and 12 patients received protocol treatment. Of the three patients who did not receive protocol treatment, one had disease progression before surgery and went hospice, and two were determined to be low risk intraoperatively. Ninety-two percent (n=11) of the patients were male with a median age of 74.5 years old (range: 52-86). Primary sites included 5 oropharynx, 3 larynx, 3 skin, and 1 oral cavity. Recurrent sites included 10 neck alone, 1 neck and larynx, and 1 neck/peristomal. The interval between recurrence and previous radiation ranged from 3.7 – 103.8 months. Cesium implant dose ranged from 60 to 70 Gy. After surgery, patients remained in the hospital 3 to 9 days (median 6 days). There were no significant toxicities, and only one patient developed superficial wound breakdown requiring local wound care. The median follow-up was 10.1 months (range: 2.6 to 23.9) after implant. At last follow up, 5 patients had recurrence: 1 local, 2 distant, and 2 with both local and distant recurrences. Of the 3 local recurrences, only 1 had in-field failure. One patient failed in the contralateral neck and one in ipsilateral neck distant from the implant. Three patients had died, 2 with recurrences and 1 died of other cause with no recurrence. Intraoperative Cesium 131 implantation after surgical resection in recurrent HNC is feasible and safe. There were no unexpected severe toxicities. Most failures were out-of-field and distant failures. Future clinical trial with combination of cesium 131 implant and immunotherapy is under development.

Carbon Ion Reirradiation for Recurrent Head and Neck Cancer: A Single-Institutional Experience

This study aimed to assess the feasibility of carbon ion reirradiation (CIR) for recurrent head and neck cancer (HNC). This retrospective study included 229 patients with recurrent HNC who were treated with CIR between 2010 and 2017. We assessed progression-free survival, overall survival, pattern of failure, and toxicity. Of the primary tumors, 54.1% were adenoid cystic carcinomas, 26.2% were squamous cell carcinomas, 8.3% were adenocarcinomas, and 11.4% were other tumor entities. The median radiation therapy interval was 3.9 years (range, 0.3-46.5 years), and patients received a median dose of 51 Gy (relative biological effectiveness [RBE]; range, 30-66 Gy [RBE]) in 3 Gy (RBE) fractions. The median cumulative lifetime dose after CIR was 132.8 Gy (range, 88.8-155.0 Gy). The median local progression-free survival after CIR was 24.2 months (95% confidence interval, 19.4-29.0 months), and the median overall survival was 26.1 months (95% confidence interval, 21.9-30.3 months). Serious acute toxicity (grade ≥3) after CIR included laryngeal edema, grade 4 (n = 2; 0.9%); dysphagia, grade 3 (n = 3; 1.3%); fistula, grade 3 (n = 1; 0.4%); and impaired hearing, grade 3 (n = 1; 0.4%). Late toxicities of grades 3 or higher (n = 18; 14.5%) included central nervous system necrosis, grades 4/3 (n = 1; 0.8%/n = 5; 4.0%); optic nerve disorder, grades 4/3 (n = 2; 1.6%/n = 2; 1.6%); impaired hearing, grade 3 (n = 5; 4.0%), osteonecrosis, grade 3 (n = 1; 0.8%); and carotid blowout, grade 4 (n = 1; 0.8%). In patients with locally recurrent HNC, CIR was a feasible, effective treatment with acceptable toxicity and good local control. Thus, CIR represented a valuable alternative to surgical salvage and palliative chemotherapy in selected patients.

Which role plays specialized palliative care in patients with relapsed and/or metastatic head and neck cancer? A retrospective analysis in Southern Switzerland.

e17503 Background: early palliative care (PC) for patients with advanced cancer improves quality of life, promotes home deaths and can improve survival. Limited data are available regarding PC in advanced head and neck cancer (HNC) patients. To investigate the effect of introducing specialized PC in patients with relapsed and/or metastatic head and neck cancer. Methods: between October 2010 and December 2018, the medical charts of all patients treated in the Oncology Institute of Southern Switzerland with relapsed and/or metastatic HNC were reviewed. Site, status of disease (metastatic at diagnosis, locally or metastatic relapsed), type and lines of treatment, treatment response and referral to specialist palliative care (yes or no) were documented. Comparisons were made between patients referred and non-referred to PC. Results: sixty-two patients with relapsed/metastatic HNC were identified, 32 (51.6%) of which were referred to specialized PC. Patients were mainly men (47, 75.8%), with a median age of 66 years (range 43 – 86). Forty-two patients (67.7%) had a metastatic disease and the most common site of tumor was the oropharynx (35.5%), followed by oral cavity (32.3%), larynx (16.1%), hypopharynx (12.9%), and unknown primary (3.2%). Forty-eight patients (77.4%) were treated with systemic treatment (75% in the PC group and 80% in the non-PC group, p = 0.638). The median overall survival was 8.1 months for all patients, 8 months for the PC group and 8.7 months for the non-PC group, without significant difference (p = 0.440). Of the deceased patients, 70% of the PC group and 73.3% of the non-PC group received chemotherapy in the last three months of life. A greater percentage of patients in the PC group died at home, but without significant difference (39.2% vs. 19%, p = 0.134). Conclusions: only half of the patient had access to specialized PC. Whereas it did not seem to affect overall survival nor influence chemotherapy prescription, it seemed to favor home deaths. Further studies investigating the impact of early PC in recurrent and/or metastatic HNC are needed to improve access to PC and maximize benefits.

Carotid dosimetry after re-irradiation with 131Cs permanent implant brachytherapy in recurrent, resected head and neck cancer.

PurposePermanent seed implant cesium-131 (131Cs) brachytherapy provides highly localized radiation for patients with recurrent head and neck cancer (HNC), who may be ineligible for external beam radiation therapy due to a high-risk of toxicity. As carotid blowout is a concern in the setting of re-irradiation, a dose to the carotid artery was examined for 131Cs brachytherapy implants.Material and methodsEleven patients were implanted with 131Cs adjacent to carotid at the time of resection for recurrent HNC. Vascularized tissue flaps were used in some patients. The carotid artery was contoured on the post-implant brachytherapy treatment plan, and the maximum carotid point dose and minimum carotid-seed distances are reported. The incidence of carotid blowout in the follow-up period was also measured.ResultsThe maximum carotid dose was 77 ±52 Gy (range, 3-158 Gy). The closest seed to the carotid artery was 0.8 ±0.8 cm (range, 0.2-2.6 cm). One patient without a flap experienced carotid blowout, which was attributed to a non-healing wound rather than to high radiation doses.ConclusionsCarotid artery doses from 131Cs are reported. Vascularized tissue flaps should be considered when planning 131Cs brachytherapy.

Target Site Analysis of Set-up and Positioning Accuracy for Head and Neck Stereotactic Ablative Radiation Therapy (SABR)

Stereotactic ablative radiotherapy (SABR) is utilized to address recurrent and/or previously irradiated head and neck cancers (HNC) and requires high set-up accuracy. We previously demonstrated excellent results with our custom cushion/mask/bite-block (CMB) immobilization system. Here, we compare set-up and positioning accuracy across different head and neck tumor locations to further optimize PTV margins for SABR treatment planning and delivery. We analyzed 375 treatment sessions across 73 patients with recurrent HNC treated with SABR using our custom CMB immobilization system. Initial set-up was performed using ExacTrac infrared tracking, and interfractional error was determined by comparing initial X-ray to the treatment plan. Patients were then shifted using ExacTrac and the residual set-up error was measured with repeat X-ray verification. Next, cone-beam CT (CBCT) was obtained and compared to ExacTrac for 3-dimensional positioning agreement. Finally, intrafractional positioning errors were measured by taking pre-beam X-ray. The data was stratified based on treatment site: paranasal sinus, nasopharynx, skull base (SB), cervical and parotid nodes (Neck), and oropharynx, oral cavity, larynx (Mucosal). The median dose and volume were 45Gy in 5 fractions (range: 27-47.5Gy, 3-5 fractions) and 17.12cm3 (range: 1.47-69.20cm3). There were no significant differences in the mean age, treatment volume, or monitor units (MU) between groups. The initial translational set-up errors were -0.3 ± 1.1mm, 0.3 ± 1.5mm, and -0.2 ± 1.4mm in the AP, CC, and LR directions, respectively. Site-specific mean 3D interfractional vectors were 2.2 ± 1.2mm (SB; P<0.00001 vs others), 2.9 ± 1.4mm (Neck), and 2.5 ± 1.7mm (Mucosal). Overall, the mean ExacTrac-CBCT agreement was between -0.1 and 0.1mm in translational and rotation directions, and overall residual errors were -0.1 ± 0.2mm, 0.0 ± 0.2mm, and 0.0 ± 0.2mm in the AP, CC, and LR directions, respectively. Site-specific mean 3D residual vectors were 0.4 ± 0.3mm (SB), 0.7 ± 0.7mm (Neck), and 0.5 ± 0.3mm (Mucosal), with a residual 3D vector >1.0mm occurring in 5.4% of SB patients compared to 26.1% (Neck) and 26.7% (Mucosal)(P=0.013). Intrafractional errors showed a mean 3D vector of 0.7 ± 0.5mm (SB; P<0.05 vs others), 1.3 ± 0.9mm (Neck), and 1.4 ± 1.5mm (Mucosal). An intrafractional 3D vector >1.0mm occurred in 16.2% of SB patients compared to 52.2% (Neck) and 46.7% (Mucosal) (P<0.0001). The calculated PTV margin for each site was ≤1.3mm (Skull Base), ≤2.2mm (Neck), and ≤3.4mm (Mucosal). In a large comparison of set-up and positioning accuracy for head and neck SABR, PTV treatment margins can be optimized depending on the treatment site. The error magnitude is significantly smaller for skull base targets and a 2-mm PTV margin may be sufficient. For mucosal targets, a 4-mm PTV margin may be necessary to account for internal organ motion.

Feasibility of reirradiation and treatment outcome in a previously irradiated territory in head-and-neck malignancies

IntroductionDespite combined modality treatment, local persistent or recurrent disease is a primary cause of treatment failure in 30–50% of patients with advanced head-and-neck cancer (HNC). The role of reirradiation is feared because of increased risk of toxicity due to the previously irradiated target volume. In the present study, we have evaluated reirradiation by image-guided intensity-modulated radiotherapy in recurrent and second primary HNCs and its outcome.Materials and methodsIn all, 24 patients with recurrence or second primary tumors in HNC were included in the study conducted between January 2009 to August 2014. All patients were treated by the image-guided intensity-modulated radiotherapy technique. The most common site of recurrence/second primary was oral tongue. The time interval between initial radiotherapy and reirradiation ranged from 8 months to 17 years.Statistical analysis usedThe association between qualitative variables was tested using the χ2-test. Statistical significance was interpreted using an arbitrary cut-off of P=0.05. Kaplan–Meier Survival graph was plotted to depict the survival pattern of the study patients.ResultsThe planning target volume volume of reirradiation ranged from 26.72 to 469.32 ml (median: 118.71 ml). Toxicity was more in patients receiving concurrent chemoradiation and in patients with less interval time between reirradiation. Out of the 24 patients, nine were no evidence of disease, eight patients expired (five disease progression, two comorbidities, and one due to hematemesis after the development of third primary), two recurred, one developed distant metastases, and four were lost to follow-up.ConclusionSurgical resection, with or without reirradiaton, provides the highest likelihood for successful salvage in locoregional (LR) recurrences in HNCs. Patients reirradiated after a long time from initial irradiation have better tolerance.

Efficacy and safety of nimotuzumab in unresectable, recurrent, and/or metastatic squamous cell carcinoma of the head and neck: A hospital-based retrospective evidence.

Context:Role of nimotuzumab in locally advanced head and neck cancer (HNC) is well established in India; however, no clinical evidence is available for its role in recurrent and/or metastatic HNC.Aims:The aim of this study is to evaluate the efficacy and safety of nimotuzumab when added to standard treatment in unresectable, recurrent, and metastatic squamous cell carcinoma of the head and neck (SCCHN).Settings and Design:Hospital records of 14 patients diagnosed with recurrent and/or metastatic HNC with histologically confirmed squamous cell carcinoma and being treated with nimotuzumab along with standard treatments from December 2010 to December 2016 were retrospectively evaluated.Subjects and Methods:The tumor response rate and overall survival (OS) were analyzed. Toxicity and adverse events (AEs) were assessed as per common terminology criteria for adverse events (CTCAE) v 4.Results:Oral cavity was most commonly involved region followed by hypopharynx and oropharynx. At 24 weeks after completion of treatment, overall response rate (complete response (CR) + partial response (PR)) was 75%. Survival rate at 1, 2, and 3 years was 77.80%, 64.81%, and 64.81%, respectively. At a median follow-up of 15.17 months, median OS was not reached. All AEs were either Grade I (66.7%) or Grade II (33.3%). No Grade III or Grade IV AEs were observed. No added toxicity was observed due to nimotuzumab.Conclusions:In the first of its kind study, the addition of nimotuzumab to standard treatment showed promising response rate as well as survival outcomes in recurrent and/or metastatic SCCHN patients without producing additional toxicity.

Patient Characteristics and Costs in Recurrent or Refractory Head and Neck Cancer: Retrospective Analysis of a Community Oncology Database

PurposeThe goal of this study was to describe patient characteristics, health resource utilization (HRU), and costs associated with treating recurrent or refractory head and neck cancer (HNC) among patients with disease progression in the community oncology setting. MethodsThis retrospective observational study was conducted by using data from the Vector Oncology Data Warehouse. Patients had been diagnosed with locally advanced or metastatic (stage III–IVc) HNC between January 1, 2007, and October 1, 2015. Patients also had evidence of at least 1 systemic anticancer therapy regimen following the diagnosis of advanced HNC, with at least 1 disease progression. Costs, treatment patterns, and HRU were evaluated beginning with diagnosis of advanced HNC through 3 lines of therapy. Costs of surgery or radiation were not available for inclusion in the analysis. Total cost for the study period and cost per month were analyzed by using a generalized linear regression model. FindingsThe study included 462 patients (median age, 61 years; range, 26–99 years); of these, 81% were male, 77% were white, and 21% were black. At initial diagnosis, the most frequent tumor locations were the hypopharynx/larynx (31%) and the oropharynx (31%). Human papilloma virus testing was most frequent among the oropharynx group (22% tested, 52% positive). Overall, 42% were current tobacco users and 22% were current or past alcohol abusers/excessive users. Platinum-based combination therapies were the most frequently administered chemotherapy in both first (42%) and second (40%) lines of treatment. Through the overall study period (mean, 20.5 months), 74% of patients were hospitalized, 19% had an emergency department visit, and 100% had an office visit. The overall mean (SD) duration of hospital stay was 12.6 days, and the median number of office visits per patient was 35. The mean monthly health care cost for the overall study period was $14,391 (95% CI, 12,739–16,044). Hospitalization costs represented ~57% of the total expenditures. Statistically significant predictors of higher overall cost included primary tumor location in the oral cavity, history of alcohol abuse/excess use, use of cetuximab, and higher comorbidity index. Older age and being stage IV versus other stages of disease at diagnosis were associated with lower overall cost. ImplicationsThese data suggest that costs of care in patients with recurrent or refractory HNC are related to patient characteristics and treatment patterns. Identification of factors contributing to the costs of care in HNC may provide a useful foundation for developing strategies to control rising costs.

A planning study for evaluation of feasibility and benefit of generalized equivalent uniform dose-assisted optimization in volumetric-modulated arc therapy for recurrent head and neck cancer

Background: Re-irradiation is effective but challenging on balancing the tumor control and late complications for recurrent head and neck cancer (HNC). The aim of this study was to investigate the feasibility of incorporating the biologically based generalized equivalent uniform dose (gEUD) objective function in the volumetric-modulated arc therapy (VMAT) treatment planning optimization process and to evaluate its benefit in such a clinical dilemma. Methods: Five recurrent HNC cases were selected. Respective original VMAT plan which fulfilled acceptable constraints was created using dose-volume (DV) optimization for each case in the first phase. Based on the DV plan, multiple corresponding plans incorporating the added single Max EUD objective for the spinal cord (SC) with stepwise stricter constraint for further biological optimization were generated for dosimetric comparison. Evaluated parameters compared between DV and DV-gEUD plans included target coverage, conformity index, homogeneity index, and sparing of organs at risk (OARs). Results: When adopting SC_gEUD90% and SC_gEUD80% as Max EUD constraint of SC, DV-gEUD optimization compared to DV optimization yielded 17.1% and 20.3%, reduction of the average D max of SC, respectively (both P value <0.05), with a non-inferior target coverage, similar conformity and slightly poorer homogeneity. The planning target volume/OAR geometry might be a factor impacting the extent of benefit provided by this gEUD-assisted optimization process. Conclusions: The method we recommended as gEUD-assisted optimization is feasible and efficient to produce better plan quality in the re-irradiation setting using VMAT for HNC to diminish the risk of myelopathy. More investigations are awaited for a better understanding of the correlation between the ɑ parameter and the OAR radiobiology.

Reirradiation in patients with recurrent head-and-neck carcinoma

Context: In head-and-neck cancers (HNCs), the incidence of recurrence after radiation therapy or the second primary tumors is 30%–50% and 20%, respectively. With an operable recurrence, surgical resection is considered the standard of care. For patients presenting with unresectable recurrence or medically unfit for surgery, definitive reirradiation with chemotherapy is the only potentially curative treatment. Aims: The aim of this study was to evaluate locoregional control (LRC), overall survival (OS), and toxicity in patients receiving reirradiation for recurrent HNCs. Subjects and Methods: Records of 35 patients reirradiated with three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT) for HNC between January 2013 and June 2015 were reviewed and analyzed. Patients were followed on a quarterly basis for 2 years. The Radiation Therapy Oncology Group morbidity criteria were employed to assess the acute and late toxicity. LRC and OS were calculated from the final day of radiation treatment using the Kaplan–Meier method. Results: The median follow-up was 14 months. The median time interval between initial radiation and reirradiation was 51 months (range 12–240 months). The median reirradiation dose was 60 Gray (Gy) (range 24–70 Gy). Eight (23%) patients underwent prior salvage surgical resection. The 1-year OS and LRC rates were 48% and 60%, respectively. Severe Grade 3-4 reirradiation-related toxicity occurred in 12 patients (34.28%). Conclusions: The present study achieved local control and OS comparable to patients with available literature. The treatment-related morbidity was higher as all patients did not receive IMRT in reirradiation setting.