Advanced Stage Oropharyngeal Cancer Research Articles

Transoral laser microsurgery for treatment of oropharyngeal cancer in 368 patients.

Oncological and functional outcome of transoral laser microsurgery (TLM) for primary treatment of oropharyngeal cancer was examined using a multimodal treatment concept. A total of 368 patients with oropharyngeal squamous cell carcinoma (pT1-4, pN0-2, M0) underwent TLM +/- neck dissection (85%), +/- (chemo)radiotherapy (57%). The majority of patients had advanced stage III and IVa disease (79%). Five-year Kaplan-Meier estimates for local control were 83.5% for pT1, 74.1% for pT2, 77.3% for pT3, and 76.0% for pT4a tumors. Five-year estimates of overall, disease-specific, and recurrence-free survival for stage I were 76.0%, 92.8%, and 69.1%; for stage II 71.1%, 85.7%, and 49.6%; for stage III 61.7%, 72.5%, and 58.8%; and for stage IVa 57.3%, 73.7%, and 63.9%, respectively. Postoperative (chemo)radiotherapy improved the outcome for advanced disease. p16-positive tumors had superior survival estimates. Overall, 93.5% maintained regular oral nutrition without feeding tube dependency. Primary TLM in multimodal concepts of treatment offers good oncologic outcome even for advanced-stage oropharyngeal cancer.

A prospective longitudinal assessment of MRI signal intensity kinetics of non-target muscles in patients with advanced stage oropharyngeal cancer in relationship to radiotherapy dose and post-treatment radiation-associated dysphagia: Preliminary findings from a randomized trial

PurposeTo assess quantitative signal intensity (SI) kinetics obtained from serial MRI of swallowing muscles as a potential imaging biomarker of radiation-induced dysphagia in oropharyngeal cancer (OPC) patients receiving radiotherapy (RT). MethodsPatients were enrolled under an IRB approved Phase II/III randomized trial. Patients underwent serial MRIs at pre-, mid-, and post-RT. Normalized T1, T1+ contrast (T1 + C), and T2 SI for swallowing muscle volumes-of-interest (VOIs) were collected and delta SI changes (Δ) were calculated. Mid- and post-RT SI relative to baseline were assessed and correlations between radiation dose and percent change in SI were calculated. Independent samples’ t-tests were used to compare the percent change of SI between patients divided into two groups based on dysphagia status post-RT. ResultsForty-six patients with stage III/IV HPV+ OPC were included in this study. Relative to baseline, mean T2 and T1 + C SIs for middle pharyngeal constrictor were both significantly higher at mid- and post-RT (p < 0.004 for all). Superior pharyngeal constrictor also showed a significant increase in T1 + C SI at mid-RT (p = 0.0004). Additional muscle VOIs showed significant changes post-RT, but not earlier at mid-RT. Both mid- and post-RT doses were significantly correlated with the percent change of normalized T2 and T1 + C SI for examined muscle VOIs (p < 0.002). Mean percent changes of normalized T2 SI at mid-RT relative to baseline for all muscle VOIs were significantly higher in patients who developed grade ≥2 dysphagia relative to patients with no/mild dysphasia (mean Δ%: 8.2% vs 1.9%; respectively, p = 0.002). However, at post-RT, these changes were only significant in T1 SI (11.2% vs −1.3%; p < 0.0001). ConclusionSignal intensity kinetics of radiation injury can be broadly correlated with the functional muscular defect. Serial MRI during the course of RT may provide an opportunity to quantitatively track muscular pathology for subclinical detection of patients at high risk to develop dysphagia.

Analysis of swallowing outcome in patients with advanced stage oropharyngeal cancer after therapy

Analysis of swallowing outcome in patients with advanced stage oropharyngeal cancer after therapy

A Dosimetric Comparison of Primary Chemoradiation Versus Postoperative Radiation for Locally Advanced Oropharyngeal Cancer.

IntroductionAdvanced-stage oropharyngeal cancer can be treated with primary chemoradiation (CRT) or primary surgery with adjuvant radiotherapy, both with similar survival outcomes. Though primary CRT prescribes a higher dose, adjuvant radiation requires irradiating the surgical bed, which may increase the high dose planned target volume (PTV). We hypothesize that the integral dose to the neck and dose to critical structures will be lower with primary CRT than adjuvant radiotherapy.MethodsWe selected the last 18 patients who underwent surgery and adjuvant radiotherapy at one institution between July 2015 and August 2016 with American Joint Committee on Cancer (AJCC) stage III or IVA oropharyngeal squamous cell cancer. Primary CRT treatment plans were created on the patients’ preoperative computed tomography (CT) scans and prescribed 70 Gy in 33 fractions, while postoperative plans were prescribed 60 Gy in 30 fractions. The radiation doses received by organs at risk for each primary CRT plan were compared to the corresponding adjuvant radiation plan.Results Primary CRT plans had significantly smaller high dose PTV than adjuvant radiation plans (187.3 cc (95% CI 134.9-239.7) and 466.3 cc (95% CI 356.7-575.9), p<0.0001). The neck integral dose was lower in 14 of 18 plans using primary CRT, although this was not statistically significant (p=0.5375). The primary CRT plans had lower mean doses to ipsilateral (31.8 Gy (95% CI 27.5-36.0) vs 39.3 Gy (95% CI 35.4-43.1), p=0.0009)) and contralateral parotid glands (22.5 Gy (95% CI 22.1-22.8) vs 27.6 Gy (95% CI 23.4-31.8), p=0.0238) and larynx (20.7 Gy (95% CI 19.3-22.2) vs 40.2 Gy (95% CI 30.8-46.6), p<0.0001).ConclusionPrimary CRT offered a decreased neck integral dose, though it was statistically insignificant. Primary CRT plans reduce mean dose to larynx and parotid glands in comparison to postoperative radiation, which may result in lower toxicities. Clinical trials comparing primary CRT and primary surgery are warranted to compare patient toxicities.

Predictors of prolongation in radiation treatment time in a veteran population treated with chemoradiation for oropharyngeal cancer

Background: Prolonged radiation treatment time (RTT) is associated with worse tumor control. Here we identify and determine the implications of factors that predict treatment prolongation in Veterans Affairs (VA) patients undergoing chemoradiation.Methods: Chart review from July 2000 to October 2013. 81 patients with advanced stage oropharyngeal cancer treated with chemoradiation.Results: Twenty-nine patients (35.8%) had RTT prolonged by ≥10 days. Prolongation mainly resulted from acute treatment toxicity (n = 22, 76%). There was no significant difference in RTT for patients treated with concurrent cisplatin versus cetuximab, or in patients treated with or without induction chemotherapy. One-/three-year locoregional control and overall survival rates of 83.4%/76.3% and 83.5%/63.6% for patients without prolonged RTT versus 61.8%/61.8% and 82.8%/73.8% for those with prolongation (p >.05).Conclusions: Prolonged RTT is a significant predictor of worse locoregional control and predominantly resulted from treatment side effects. More aggressive regimens with induction and concurrent chemotherapy did not predispose to prolonged RTT.

Low rates of contralateral neck failure in unilaterally treated oropharyngeal squamous cell carcinoma with prospectively defined criteria of lateralization

Unilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low-volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced-stage oropharyngeal cancer undergoing unilateral RT. Thirty-seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected. At median follow-up of 32 months, 3-year locoregional control, contralateral regional failure, distant metastasis-free survival, and disease-free survival were 96%, 0%, 7%, and 93%, respectively. Low rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.

Impact of Concurrent Chemoradiation on T Cell Populations in Patients With Advanced-Stage Oropharyngeal Squamous Cell Carcinoma: Immunology and Immunotherapy

Concurrent chemoradiation (CRT) is commonly used to treat advanced stage oropharyngeal cancer (OPC). CRT affects the immune system, but the specific effects on immune cell populations and function during and after treatment are poorly defined. This study was performed to assess the impact of CRT on T cell populations and their function during and after treatment in patients with advanced stage OPC.

Survival Analysis of Patients With Advanced-Stage Oropharyngeal Cancer Stratified by Molecular Profile and Treatment: Survivorship

Purpose/Objective(s): To determine differences in survival outcomes in patients with advanced stage oropharyngeal squamous cell carcinoma (OPSCC) when stratified by treatment and molecular profile. Materials/Methods: Demographic, pathologic and survival data was obtained from all patients diagnosed and treated for OPSCC from 1998-2010 at a tertiary care center (University of Alberta). Tissue microarrays (TMAs) were constructed to include all patients treated within this time frame with sufficient pathologic specimen available (nZ334). TMAs were stained by immunohistochemistry for p16, EGFR, Ki-67, Bcl-XL and p53, and digitally quantified in comparison to positive and negative controls. Patients were stratified by molecular profile using standardized expression cutoffs. Molecular profiles were then used to stratify patients who received the following treatment modalities: 1) primary surgery + chemoradiation (S+CRT), 2) primary surgery + post-operative radiation (S+RT) and 3) primary chemoradiation +/salvage surgery (CRT). Disease-specific (DSS) and overall survival was calculated for each stratum using Kaplan-Meir analysis. Hazard ratios and multivariate analysis was performed using Cox regression. Results: Distinct twoand five-year survival curves were obtained for each treatment stratum. When considering p16 status, 5-year DSS was highest for patients who received S+CRT (84.8% for p16+ and 60.8% for p16-), followed by S+RT (77.5% for p16+ and 54% for p16-) and CRT (55.2% for p16+ and 38.1% for p16-). Remarkably, the 5-year DSS of patients treated with S+CRT with low tumor EGFR levels was 100%. Patients with p53 positivity had improved DSS with surgical modalities. Bcl-XL levels alone were not associated with a significant difference in survival outcome. Elevated Ki-67 levels were associated with improved outcomes in patients receiving radiation therapy but low Ki-67 levels stratified patients into the poorest outcome group with a 5-year DSS of 18%. Conclusions: To our knowledge, this represents the largest cohort of advanced stage OPSCC survival comparing surgical and non-surgical treatment modalities, stratified by clinically significant biomarkers. Triple modality therapy provides optimal survival outcomes for patients with advanced stage OPSCC regardless of molecular profile. Author Disclosure: V.L. Biron: None. D.A. O’Connell: None. A.C. Klimowicz: None. L. Puttagunta: None. J. Harris: None. H. Seikaly: None.

Transoral Laser Microsurgery as Primary Treatment for Advanced-Stage Oropharyngeal Cancer: A United States Multicenter Study

Transoral Laser Microsurgery as Primary Treatment for Advanced-Stage Oropharyngeal Cancer: A United States Multicenter Study

8540 POSTER The Treatment Result of Advanced Stage Oropharyngeal Cancer by Radiotherapy With or Without Chemotherapy – the Impact of Intensity Modulation Radiotherapy and FDG-PET

8540 POSTER The Treatment Result of Advanced Stage Oropharyngeal Cancer by Radiotherapy With or Without Chemotherapy – the Impact of Intensity Modulation Radiotherapy and FDG-PET

Swallowing function after transoral laser microsurgery (TLM) ± adjuvant therapy for advanced-stage oropharyngeal cancer.

To perform a longitudinal description of swallowing function following transoral laser microsurgery (TLM) ± adjuvant therapy for advanced-stage oropharyngeal cancer (OPC) and identify prognostic factors associated with swallowing performance. Retrospective analysis and longitudinal descriptive study of swallowing outcomes. Patients treated with TLM for AJCC stage III-IV OPC at Washington University from 1996 to 2008 were included. A search of medical records and direct patient contact were performed to obtain swallowing function at multiple time points. Persistently poor swallowing at 2 year after surgery was the primary outcome measure. Two year swallowing outcomes stratified by tumor site and T stage are presented. One hundred eighteen patients met criteria for the study (median follow-up 53.9 months). There were 44 T1's, 41 T2's, 23 T3's and 10 T4's. Forty seven percent received radiotherapy and 41% received chemoradiotherapy. Ninety-eight percent underwent neck dissection. Patients tolerated TLM well with 82% enjoying good swallowing at 1 month after surgery. During adjuvant therapy, at 3 months, good swallowing dropped to 55%. At 1 and 2 years after TLM, 89% and 88% of patients had good swallowing function, respectively. At 2 years, 9 patients had persistently poor swallowing function. 93% of patients with T1 through T3 enjoyed good swallowing at 2 years. T4 base of tongue disease was associated with persistently poor swallowing function in multivariate analyses (P = 0.0023), with 40% having good swallowing at 2 years. Preexisting comorbidities and conversion to an open procedure were associated with delayed return of swallowing function, but not with persistently poor swallowing. Seven patients developed late-onset swallowing dysfunction. Treatment of advanced stage OPC with TLM ± adjuvant therapy results in excellent swallowing outcomes for patients with either T1 to T3 tonsil or T1 to T3 base of tongue resections. A detailed, longitudinal swallowing profile is presented to assist in preoperative counseling.

Transoral Laser Microsurgery (TLM)±Adjuvant Therapy for Advanced Stage Oropharyngeal Cancer: Outcomes and Prognostic Factors

Transoral Laser Microsurgery (TLM)±Adjuvant Therapy for Advanced Stage Oropharyngeal Cancer: Outcomes and Prognostic Factors

P8 Extended vertical lower trapezius island myocutaneous. flap for repairing oropharyngeal defects following radical surgery for patients with advanced-stage oropharyngeal cancer

P8 Extended vertical lower trapezius island myocutaneous. flap for repairing oropharyngeal defects following radical surgery for patients with advanced-stage oropharyngeal cancer

Swallowing Function After Chemoradiation for Advanced Stage Oropharyngeal Cancer

Swallowing Function After Chemoradiation for Advanced Stage Oropharyngeal Cancer

Swallowing Function After Chemoradiation for Advanced Stage Oropharyngeal Cancer

Advanced-stage oropharyngeal cancer may be treated either surgically or nonsurgically. We reported previously functional outcomes after surgical resection with free-tissue transfer. In the present study, we evaluated swallowing function after combined chemoradiation for oropharyngeal cancer. Retrospective review of 30 patients treated at a tertiary academic center for Stage III/IV oropharyngeal cancer with sequential or concurrent chemoradiation from 1994 to 2003. Inclusion criteria were met by 27 of 30 (90%) patients. Most patients had base of tongue lesions (67%) and Stage IV disease (93%). Gastrostomy was carried out in 22 (82%) patients either before or during treatment. Three months after chemoradiation, 33% (9/27) were consuming all nutrition orally, 22% (6 of 27) were NPO, and 45% (12 of 27) had some oral intake but still required tube feeds. One year after treatment, 53% (10 of 19) had an exclusively oral diet whereas 47% still required tube feeds including 1 patient (5%) who was NPO. In patients without recurrence and follow-up length >1 year, 69% (9 of 13) were consuming all nutrition orally whereas 31% still required gastrostomy tube (G-tube) support. A higher rate of G-tube dependence was observed in patients treated for base of tongue lesions vs tonsil lesions (67% vs 25%, P = 0.049, chi(2) analysis). At this institution, the short-term (3-4 months) rate of G-tube dependence was similar after surgical and non-surgical treatment of oropharyngeal cancer. One year after chemoradiation, 31% of patients without recurrence still required tube feeds. These results suggest that organ-preservation protocols do not reduce the prevalence of chronic dysphagia and G-tube dependence after management of oropharyngeal cancer. C-4.

Swallowing function after chemoradiation for advanced stage oropharyngeal cancer

Objectives: Advanced stage oropharyngeal cancer may be treated either surgically or nonsurgically. We previously reported functional outcomes following surgical resection with free-tissue transfer. In the present study, we evaluated swallowing function after combined chemoradiation for oropharygeal cancer. Methods: Retrospective review of 30 patients treated at a tertiary academic center for stage III/IV oropharyngeal cancer with sequential or concurrent chemoradiation from 1994–2003. Results: Inclusion criteria were met by 27/30 (90%) patients. Most patients had base of tongue lesions (67%) and stage IV disease (93%). Gastrostomy was performed in 22 (82%) patients either before or during treatment. Three months after chemoradiation, 33% (9/27) were consuming all nutrition orally, 22% (6/27) were NPO, and 45% (12/27) had some oral intake but still required tube feeds. One year after treatment, 53% (10/19) had an exclusively oral diet and only 1 patient (5%) was NPO. In patients without recurrence and follow-up length >1 year, 69% (9/13) were consuming all nutrition orally while 31% still required G-tube support. Conclusions: Long-term dysphagia is common following both surgical and nonsurgical treatment of advanced-stage oropharyngeal SCCA.

Swallowing function and tracheotomy dependence after combined-modality treatment including free tissue transfer for advanced-stage oropharyngeal cancer.

There are many treatments available for advanced oropharyngeal cancer. Organ-sparing protocols reserve surgery for salvage and are thought to provide adequate rehabilitation. Surgical resection with free tissue transfer may also provide adequate functional rehabilitation. The objective was to describe swallowing status and time to decannulation in a series of patients treated with combined-modality therapy that included free flap reconstruction. Retrospective chart review. Patient data were obtained from medical records of 20 patients with stage III or IV oropharyngeal carcinoma, who were consecutively treated with surgical tumor extirpation, free flap reconstruction, and postoperative irradiation at a tertiary academic center from 1985 to 2002. The following variables were identified: patient and tumor characteristics, free flap type, irradiation data, and airway and swallowing status before and after treatment. One patient underwent total laryngopharyngectomy, and the remaining 19 patients underwent tracheotomy at the time of definitive surgery. Free flap reconstructions included 1 ulnar and 15 radial forearm fasciocutaneous flaps and 4 fibula osteocutaneous flaps. Postoperatively, all 19 tracheotomized patients had successful decannulation. Average time to decannulation was 15 days (range, 3-42 d). After surgery and before irradiation, 13 patients initiated oral intake, on average, at 19.5 days (range, 7-28 d); 6 patients required no additional supplementation. By 4 months after surgery, having completed radiation therapy, 10 patients were consuming all nutrition orally; the other 10 patients still required tube-feed supplementation, although 6 of these patients were also eating by mouth. Combined-modality treatment that includes free flap reconstruction for advanced-stage oropharyngeal cancer may provide reasonable functional rehabilitation with respect to postoperative airway and swallowing.

Post-operative radiation therapy for advanced-stage oropharyngeal cancer.

Between 1985 and 1999, 43 patients with locally-advanced, resectable oropharyngeal cancer were treated with combined surgery and post-operative radiation therapy (RT) at Oregon Health and Science University. Five patients (12 per cent) had Stage III disease and 38 patients (88 per cent) had Stage IV disease. All patients had gross total resections of the primary tumour. Thirty-seven patients had neck dissections for regional disease. RT consisted of a mean tumour-bed dose of 63.0 Gy delivered in 1.8-2.0 Gy fractions over a mean of 49 days. At three- and five-years, the actuarial local control was 96 per cent and the actuarial local/regional control was 80 per cent. The three- and five-year actuarial rates of distant metastases were 41 per cent and 46 per cent, respectively. The actuarial overall survival at three- and five-years was 41 per cent and 34 per cent, respectively. The actuarial rates of progression-free survival were 49 per cent at three-years and 45 per cent at five years. Combined surgery and post-operative RT for advanced-stage oropharyngeal cancer results in excellent local/regional control. This particular group of patients experienced a high-rate of developing distant metastases.