Organ Preservation Therapy Research Articles

Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer: It Does Not Always Fade With Time

head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92:4-14, 2009 17. Kies MS, Holsinger FC, Lee JJ, et al: Induction chemotherapy and cetuximab for locally advanced squamous cell carcinoma of the head and neck: Results from a phase II prospective trial. J Clin Oncol 28:8-14, 2009 18. Vermorken JB, Mesia R, Rivera F, et al: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359:1116-1127, 2008 19. Vokes EE, Stenson K, Rosen FR, et al: Weekly carboplatin and paclitaxel followed by concomitant paclitaxel, fluorouracil, and hydroxyurea chemoradiotherapy: Curative and organ-preserving therapy for advanced head and neck cancer. J Clin Oncol 21:320-326, 2003 20. Fu KK, Pajak TF, Trotti A, et al: A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: First report of RTOG 9003. Int J Radiat Oncol Biol Phys 48:7-16, 2000 21. Trotti A, Fu KK, Pajak TF, et al: Long term outcomes of RTOG 90-03: A comparison of hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinoma Int J Radiat Oncol Biol Phys 63:S70–S71, 2005 (suppl) 22. Brockstein B, Haraf DJ, Rademaker AW, et al: Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: A 9-year, 337-patient, multi-institutional experience. Ann Oncol 15:1179-1186, 2004

Idiopathische spontane Milzarterienruptur

Hemoperitoneum due to spontaneous rupture of a visceral vessel may result from a variety of underlying pathologies. However, its idiopathic form does not show evidence of any predisposition. An abdominal CT scan for acute abdominal pain yielded the unexpected diagnosis of a ruptured splenic artery in a 21-year-old patient. Hemostasis was achieved by endovascular coiling of a segmental splenic artery lacking any evidence of pathological transformation. An extensive intraabdominal hematoma was evacuated in a consecutive laparoscopy which, furthermore, confirmed interventional success. Despite extensive diagnostic efforts, the cause of the bleeding remained undefined. Spontaneous hemoperitoneum may occasionally be considered as a cause of acute abdomial pain and is diagnostically challenging. An interdisciplinary approach is desirable to meet the objective of modern organ-preserving therapy in splenic artery rupture.

A Feasibility Study of Parametric Response Map Analysis of Diffusion-Weighted Magnetic Resonance Imaging Scans of Head and Neck Cancer Patients for Providing Early Detection of Therapeutic Efficacy

The parametric response map (PRM) was evaluated as an early surrogate biomarker for monitoring treatment-induced tissue alterations in patients with head and neck squamous cell carcinoma (HNSCC). Diffusion-weighted magnetic resonance imaging (DW-MRI) was performed on 15 patients with HNSCC at baseline and 3 weeks after treatment initiation of a nonsurgical organ preservation therapy (NSOPT) using concurrent radiation and chemotherapy. PRM was applied on serial apparent diffusion coefficient (ADC) maps that were spatially aligned using a deformable image registration algorithm to measure the tumor volume exhibiting significant changes in ADC (PRM(ADC)). Pretherapy and midtherapy ADC maps, quantified from the DWIs, were analyzed by monitoring the percent change in whole-tumor mean ADC and the PRM metric. The prognostic values of percentage change in tumor volume and mean ADC and PRM(ADC) as a treatment response biomarker were assessed by correlating with tumor control at 6 months. Pixel-wise differences as part of PRM(ADC) analysis revealed regions where water mobility increased. Analysis of the tumor ADC histograms also showed increases in mean ADC as early as 3 weeks into therapy in patients with a favorable outcome. Nevertheless, the percentage change in mean ADC was found to not correlate with tumor control at 6 months. In contrast, significant differences in PRM(ADC) and percentage change in tumor volume were observed between patients with pathologically different outcomes. Observations from this study have found that diffusion MRI, when assessed by PRM(ADC), has the potential to provide both prognostic and spatial information during NSOPT of head and neck cancer.

Utility of the gastro-omental free flap in head and neck reconstruction

In the current era of organ-preservation therapies, surgical salvage and reconstruction of defects following ablation of mucosa and soft tissue in the head and neck is extremely challenging because of the toxic effects of chemoradiation and intensive radiotherapy on wounds. The anatomical, physiological and immunological properties of the gastro-omental flap make it an ideal reconstructive technique in head and neck surgery. Several case series published in the past 12 months highlight the utility of this flap in inhospitable wounds and particularly in restoration of circumferential pharyngeal defects. The gastro-omental flap produces satisfactory functional results and morbidity in this group of high-risk patients. The gastro-omental free flap provides an alternative to traditional reconstructive techniques that is ideally suited to high-risk complex wounds in the head and neck.

Conservative Treatment of Invasive Bladder Cancer

The concept of organ-preserving therapies is a trend in modern oncology, and several tumour types are now treated in this fashion. Trimodality therapy consisting of as thorough a transurethral resection of the bladder tumour as is judged safe, followed by concomitant chemoradiation therapy, is emerging as an attractive alternative for bladder preservation in selected patients with muscle-invasive bladder cancer. Long-term data from multiple institutional and cooperative group studies have shown that this approach is safe and effective and that it provides patients with the opportunity to maintain an intact and functional bladder with a survival rate similar to that for modern radical cystectomy.

Transoral Robotic Surgery (TORS) in Laryngeal and Hypopharyngeal Cancer

The current trend in managing laryngeal and hypopharyngeal cancer is to perform organ preservation therapy, which improves quality of life and decreases treatment-related morbidity. Transoral robotic surgery (TORS) can overcome the limit of "line of sight" often met in classic transoral procedure. We utilized a robotic surgical system to evaluate the feasibility and oncologic safety of transoral partial pharyngectomy and laryngectomy. TORS was performed by using a "da Vinci surgical robot" (Intuitive Surgical, Inc., Sunnyvale, CA). An FK retractor (Gyrus Medical Inc., Maple Grove, MN) was used to expose the cancerous lesion transorally, and an endoscopic arm was introduced through the oral cavity with two instrument arms placed 30 degrees apart from the endoscopic arm. We performed TORS on 1 patient with pyriform sinus carcinoma and 4 patients with glottic carcinoma as a prospective human trial. Average surgical time measured was 39 minutes, including an average of 25 minutes used for locating the robotic surgical system in place and exposing the lesion. TORS can provide a magnified three-dimensional view and overcome the limitation resulting from the "line of sight" that hinders the classic transoral procedure. All surgical resection margins were free of carcinoma. There were no perioperative complications, and also, no mortality due to the surgical procedure. This study demonstrates that the application of TORS for partial pharyngectomy and partial laryngectomy is technically feasible and safe.

Feasibility of transoral lateral oropharyngectomy using a robotic surgical system for tonsillar cancer

Conventional surgical approaches for tonsillar carcinomas have a great risk for developing treatment-related morbidity. To minimize this morbidity, transoral lateral oropharyngectomy (TLO) using the robotic surgical system was performed, and the efficacy and feasibility of this procedure was evaluated. TLO was performed using the da Vinci surgical robot (Intuitive Surgical, Inc., Sunnyvale, CA). It consists of a surgeon's console and a manipulator cart equipped with three robotic arms. The surgeon is provided with three-dimensional magnified images from the endoscopic arm and can control two instrument arms for delicate operations from the console. Safe resection of tonsillar carcinoma was possible with the three-dimensional magnified images. When proceeding with resection of the buccopharyngeal fascia, we could prevent damage to the carotid artery, which is located posterolateral to the tonsillar fossa, since the joint at the distal part of the robotic arm can be bent freely from side to side. By using the 30 degrees endoscope, we can achieve a better surgical view of the base of the tongue area. TLO was performed successfully in all five patients without surgical complications. The mean operating time was 44 min, and an average of 19 min was required for setting up the robotic system. TLO using the robotic system will be a good option for organ preservation therapy in the treatment of carcinomas of the tonsil and the tonsillar fossa in the future.

Squamous cell carcinoma of the penis.

Squamous cell carcinoma of the penis is a rare disease in Western countries. In geographical locations where infantile circumcision is not routinely practised and genital hygiene is poor, penile cancer may comprise 10-20% of all malignancies. Superficial tumours (Ta-Tl) should be treated with organ-preserving therapy. Partial of total penectomy is recommended for invasive penile carcinoma (stage T2 or higher). Currently, management of the ilioinguinal lymph nodes is controversial. The value of radiation therapy and chemotherapy is still uncertain; these treatments are only palliative therapy modalities.

The Treatment Outcome of Hypopharynx Cancer: Surgery versus Organ Preservation Therapy

Background and Objectives Hypopharynx cancer usually presents with late stage diseases requiring radical resection including total laryngectomy with reconstruction resulting in severe functional deficits. In order to preserve organ function, chemotherapy in combination with radiotherapy was introduced and it showed similar treatment. The aim of this study is to compare the treatment outcomes of surgery and organ preservation therapy. Subjects and Method A retrospective review of 55 patients who were diagnosed with hypopharynx cancer and underwent curative treatment from 1994 to 2006 was performed. Patients who underwent surgery or surgery plus postoperative radiotherapy were assigned to surgical treatment group and patients who underwent radiotherapy or radiotherapy with chemotherapy were assigned to organ preservation therapy group. Results Surgical treatment group consisted of 29 patients (52.7%) and organ preservation therapy group consisted of 26 patients (47.3%). The overall 5 year survival rate was 34%. The survival rate was decreased significantly according to the N stage (p=0.02). There was no statistically significant difference in 5 year survival rates between the two groups. The larynx preservation rate was 35.8% for the organ preservation therapy group and 44% for the conservation surgery group. Conclusion Treatment of hypopharynx cancer could be individualized according to the status of diseases.

Feasibility of Robotic Surgical System in the Field of Head and Neck Surgery

The current trend in managing head and neck cancer is to perform organ preservation therapy which improves quality of life and decreases treatment related morbidity. Transoral robotic surgery (TORS) can overcome the limit of line of sight often met in classic transoral procedure. We utilized robotic surgical system for the treatment of oropharyngeal, hypopharyngeal and laryngeal cancer. TORS was performed using the da Vinci surgical robot (Intuitive Surgical, Inc., Sunnyvale, CA). It is consisted of a surgeon’s console and a manipulator cart equipped with 3 robotic arms. The surgeon is provided with 3-dimensional magnified images from the endoscopic arm and can control 2 instrument arms for delicate operations from the console. TORS can provide magnified three dimensional views and overcome the limitation resulting from the line of sight which hinders classic transoral procedure. Safe resection of the head and neck cancer lesion was possible with the 3-dimensional magnified images and two robotic arms which have 360 degree joint motion. The application of TORS for lateral oropharyngectomy, partial hypopharyngectomy and partial laryngectomy is technically feasible and safe.

Impact of fdg-pet/ct fused imaging on tumor volume assessment of head-and-neck squamous cell carcinoma: intermethod and interobserver variations

Although gross tumor volume (GTV) at the primary site can predict local control of head-and-neck squamous cell carcinoma (SCC) in patients who are treated with organ-preservation therapy, GTV assessment does not eliminate substantial interobserver variation. To evaluate whether F-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) fused imaging provides additional information for GTV assessment. We obtained FDG-PET/CT fused images on 20 patients with head-and-neck SCC. All had undergone preoperative conventional workup, including contrast-enhanced CT and magnetic resonance imaging (MRI). The GTV of the primary tumors was designed by two independent observers who used routine clinical data. Observer A was a radiologist and observer B a radiation oncologist. GTV1 and GTV2 were designed without and with FDG-PET/CT, respectively. For geometric interobserver comparison, we calculated the concordance rate as the ratio of the intersection (AxB) of the GTVs to their union (AxB). Intermethod (GTV1 vs. GTV2) and interobserver (A vs. B) differences in the GTVs were assessed by Bland-Altman analysis and the Spearman rank-correlation test. The interobserver concordance rates for GTV1 and GTV2 were compared using a two-tailed paired-samples t test. On FDG-PET/CT, all primary tumors were visualized. There was no systemic trend for a volume difference between GTV1 and GTV2. Although the 95% limits of agreement were wider for interobserver than intermethod differences, the 95% limits of interobserver agreement were narrower for GTV2 than GTV1. The mean interobserver concordance rate for GTV2 was higher than for GTV1 (54.5% vs. 39.1%, P=0.0002). FDG-PET/CT is a useful modality for consistent GTV assessment, which should not be used as a single modality but rather to obtain supplemental information in patients with head-and-neck SCC.

Management of superficial recurrences in an irradiated bladder after combined-modality organ-preserving therapy: Weiss C, Wittlinger M, Engehausen DG, Krause FS, Ott OJ, Dunst J, Sauer R, Rödel C, Department of Radiation Therapy, University of Erlangen, Erlangen, Germany.

Standard treatment for superficial bladder cancer is transurethral resection of the bladder tumor (TURBT) followed by intravesical therapy. Little is known about the biologic behavior and treatment response of superficial disease within an irradiated bladder. We specifically analyzed patients who developed superficial recurrence after TURBT and radiotherapy or radiochemotherapy. Between 1982 and 2006, a total of 531 consecutive patients with invasive bladder cancer were treated by using various bladder-sparing protocols at our institution. Of these, 389 (76%) achieved a complete response after TURBT and radiotherapy/radiochemotherapy. During follow-up, 68 of 389 patients (17%) developed a superficial local relapse (≤T1) and form the subject of this study. Sixty-four of 68 patients underwent conservative TURBT with or without intravesical treatment (4 patients underwent immediate cystectomy): 31 of 64 patients (48%) had no further bladder recurrence, 21 (33%) experienced additional superficial recurrences, and 12 (19%) ultimately progressed to muscle-invasive disease. Disease-specific survival rates were 87% and 72% at 5 and 10 years, respectively. Compared with 255 patients without local bladder relapse after primary treatment, no significant difference was found for disease-specific survival rates (72% after superficial vs. 79% without local relapse at 10 years, P = 0.78). However, significantly fewer patients with a superficial relapse survived with their native bladder (50% after superficial vs. 76% without local relapse at 10 years, P < 0.001). A further bladder-sparing approach with TURBT and intravesical therapy is reasonable for patients with superficial relapse after combined-modality treatment without compromising survival. However, these patients are at greater risk of requiring late cystectomy.

Laryngeal transplantation: research, clinical experience, and future goals.

The loss of a functional voice because of trauma or laryngectomy can have a devastating impact on a patient's self-esteem and overall quality of life. Unfortunately, even with advances in organ preservation therapy, total laryngectomy is frequently necessary in the treatment of laryngeal carcinoma. Over the past several years, the senior author initiated research into laryngeal transplantation with the goal of restoring lung-powered speech for these patients. The research led to the development of an animal model and several groundbreaking studies in this area. Investigations into the use of irradiation, single-drug and multidrug immunosuppression, and the effects of mammalian target of rapamycin (mTOR) inhibitors have produced significant insight into laryngeal allograft preservation. The laboratory research culminated in the first successful total laryngeal transplant in 1998. The patient had suffered significant laryngeal trauma and strongly desired return of laryngeal phonation. The patient has been maintained on multidrug immunosuppression with minimal difficulties. Now more than 8 years after the procedure, the patient continues to have an excellent voice and dramatically improved quality of life. Recent data suggest that altered immunosuppression schedules and the use of mTOR inhibitors may allow patients to minimize immunosuppression-related adverse effects and ameliorate the risk of developing recurrent or de novo carcinoma. These data, when considered in combination with the progress made over the past 14 years, lead us to believe that the future of laryngeal transplantation is bright.

Management of Superficial Recurrences in an Irradiated Bladder After Combined-Modality Organ-Preserving Therapy

Standard treatment for superficial bladder cancer is transurethral resection of the bladder tumor (TURBT) followed by intravesical therapy. Little is known about the biologic behavior and treatment response of superficial disease within an irradiated bladder. We specifically analyzed patients who developed superficial recurrence after TURBT and radiotherapy or radiochemotherapy. Between 1982 and 2006, a total of 531 consecutive patients with invasive bladder cancer were treated by using various bladder-sparing protocols at our institution. Of these, 389 (76%) achieved a complete response after TURBT and radiotherapy/radiochemotherapy. During follow-up, 68 of 389 patients (17%) developed a superficial local relapse (< or = T1) and form the subject of this study. Sixty-four of 68 patients underwent conservative TURBT with or without intravesical treatment (4 patients underwent immediate cystectomy): 31 of 64 patients (48%) had no further bladder recurrence, 21 (33%) experienced additional superficial recurrences, and 12 (19%) ultimately progressed to muscle-invasive disease. Disease-specific survival rates were 87% and 72% at 5 and 10 years, respectively. Compared with 255 patients without local bladder relapse after primary treatment, no significant difference was found for disease-specific survival rates (72% after superficial vs. 79% without local relapse at 10 years, p = 0.78). However, significantly fewer patients with a superficial relapse survived with their native bladder (50% after superficial vs. 76% without local relapse at 10 years, p < 0.001). A further bladder-sparing approach with TURBT and intravesical therapy is reasonable for patients with superficial relapse after combined-modality treatment without compromising survival. However, these patients are at greater risk of requiring late cystectomy.

Functional morbidities in patients ≥ 65 years compared with younger patients undergoing organ preservation therapy (OPT) for squamous cell carcinoma (SCC) of larynx (L) or propharynx (OP)

16533 Background: Advanced age is shown to be associated with increased late toxicity and minimal clinical benefit in head and neck cancer patients receiving aggressive or combined modality therapies. Elderly may also have delayed functional recovery after OPT. We conducted a retrospective study in patients = 65 years with L or O SCC undergoing OPT to compare functional outcome/ recovery with younger patients undergoing similar treatment. Methods: Patients with L or O SCC from January 1996-January 2006 who underwent OPT were retrospectively studied and stratified into 2 groups: = 65 or &lt; 65 years based on age at diagnosis. Dysphagia, gastrostomy (g) tube dependence, speech quality and weight loss at diagnosis, 3 and 9 months post therapy were compared. Swallowing and speech were evaluated by 2 specially trained therapists based on the Swallowing Performance Scale and GBRAS Scale (perceptual impression of voice quality) respectively. Student z-test and t-test were used in statistical analysis for comparison between patient proportion and mean values. Results: One hundred and twenty patients (L 74 and OP 46) received OPT, of which 43 were excluded (recurrence/inadequate records). Of the 77 (L 54 and O 23) patients analyzed (KPS 80–100), 44 (57%) were = 65 and 33 (43%) &lt;65; more patients aged &lt;65 had advanced stage; 14 patients (31%) = 65 and 16 (48%) &lt;65 received CRT or altered fractionation RT, rest of the patients received standard RT. Elderly group had greater proportion of patients with continued weight loss and higher incidence of dysphonia (70% vs 43% z-score 2.97, p=0.003) at 3 and 9 months than younger patients. Of 19 patients in the elderly group with g-tube, 13 were g-tube dependant at 3 months (68%) vs 12/23 (52%) in the younger population. Conclusions: Elderly may have persistent functional morbidity compared to younger patients receiving similar OPT. As the goal of OPT is to improve functional outcome, careful assessment of risk benefit ratio in the elderly is warranted before administering aggressive therapies. No significant financial relationships to disclose.

Squamous Cell Head and Neck Cancer

This book is part of the Current Clinical Oncology series and is preceded by 14 other topics, notably the common tumours of lung, breast and colorectal as well as more diverse subjects such as hepatocellular carcinoma, myeloma and intra-operative irradiation. Now it is the turn of squamous cell head and neck cancer. This is a multi-author book written by 48 medical/radio oncologists and unashamedly American in perspective with only one author from Europe (Jacques Bernier) and four from the National Cancer Institute of Singapore. In terms of the target audience, this is a studious work with few illustrations, produced in dense type and replete with references. It is a treasure trove for the student writing a paper or applying for a grant but not an easy read. The book does not deal with broad issues and is likely to confuse the uninitiated. The first chapter deals with risk factors for head and neck cancer of those in the population that do not smoke or drink. This small cohort of patients has attracted attention because of the association with human papilloma virus and the potential for a vaccine solution. Other factors addressed are relatively inconsequential such as diet, genetic predisposition, immune deficiency, etc. The next four chapters deal with surgical topics: the first is laryngeal preservation surgery, which is a well-established subject – nothing much new here. The next topic is laser therapy, where the European results of larynx and oropharyngeal surgery are noteworthy. The following chapter discusses the role of neck dissection in the context of organ preservation therapy. The issue is whether a patient with positive cervical lymphadenopathy needs a complete neck dissection after chemoradiation. The answer is that this is only necessary for patients with disease greater than N1. The third chapter deals with surgical salvage after failed chemoradiation (organ preservation therapy) and here there may be a surveillance role for PET in detecting persistent disease. We will have to wait for the answer. Chapters 6–10 deal with radiotherapy issues; first, the management of the T3–T4 tumour of the larynx. The authors provide a wealth of detail on the subject and conclude that careful case selection is important for the outcome. The next chapter deals with brachytherapy, a subject with a long history but again there is little new to report. In chapter 8, intensity-modulated radiation therapy is described but it is too early to expect a realistic account of its performance. However, the next chapter on accelerated and hyperfraction radiation therapy does provide answers within the final analysis – an assertion that the more radiation targeted on the tumour, the greater is the chance of cure. The remaining half of the book covers medical oncology. The role of traditional induction chemotherapy is dispatched quickly but its application in organ preservation is fully developed in the succeeding two chapters. These convey the reality of a fast-moving topic breaking new ground, where the advantage now lies with multimodality therapy. Concomitant chemoradiation gives up to an 8% improvement in survival across all stages of disease. Nevertheless, there is a catch as it does not extend to all age groups, as by the age of 70 years the survival advantage is lost. Chapters 16–19 deal with novel therapies including attempts to protect normal tissue from radiation damage and new therapy targeted at neovascularisation, cell cycle pathways and gene manipulation. Herein lie the innovations for the future and studies are already being designed to trial these molecules in the head and neck. It would be prescient for surgical oncologists to digest the chemoradiation chapters if they want to be prepared for impending environmental change. All in all, this is a book packed with data giving glimpses of the future. It is a must for insomniacs.

Function and organ preservation in adult cancers of the head and neck

Treatment for primary head and neck cancer has evolved from the use of radical approaches to therapies preserving important functions. Essential to this concept is the maintenance of therapeutic efficacy. The advances of organ-sparing surgery, improved radiation techniques and fractionation, and the addition of chemotherapy and targeted systemic agents, have added to the number of patients who undergo organ-preservation therapy. Crucial functions that can be spared include speech, swallowing, vision, salivation and cosmesis. This paper examines advances in therapy that allow the preservation of these important functions, scenarios where organ and function preservation is indicated, given current technology and agents, and where there might be future improvements.

Altered fractionation: a fractional benefit?

A major shift in the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) has taken place in the past two decades. Since the Veterans Affairs Larynx Study showed that cisplatin/5-fluorouracil chemotherapy plus radiation is an effective treatment for larynx cancer, radiation-based organ-preservation therapy has become a mainstay of treatment for HNSCC around the world.1–4

P159 Salvage Surgery After Organ Preservation Therapy in Patients With Stage III or IV Head and Neck Squamous Cell Carcinoma

P159 Salvage Surgery After Organ Preservation Therapy in Patients With Stage III or IV Head and Neck Squamous Cell Carcinoma

Advanced‐staged tonsillar squamous carcinoma: Organ preservation versus surgical management of the primary site

Our aim was to review our experience in the management of advanced tonsillar squamous cell carcinoma (SCC) and to compare treatment outcomes between patients treated with and without surgery to the primary site. The records of 74 patients with advanced-stage tonsillar SCC were reviewed. The median age at diagnosis was 58 years. Thirty-eight patients received definitive surgery to the primary site, and 36 were treated with an organ-preservation approach (OP) using radiotherapy +/- chemotherapy. No significant difference in overall survival (OS) or freedom from relapse (FFR) by treatment was found. T classification and N status were significant independent predictors on multivariate analysis for OS and FFR. Major late toxicity was noted in 10 patients in the surgical group and nine in the OP group. Patients treated with OP and primary surgery had comparable OS and FFR. T classification and N status were significant independent predictors for tumor relapse and survival. On the basis of these results, we favor organ-preservation therapy for patients with advanced-stage tonsillar SCC.