Head & Neck Cancer: Encouraging Research Roundup from Multidisciplinary Symposium

Head/Neck Cancer SymposiumAmong the research findings presented at the Multidisciplinary Head and Neck Cancer Symposium were studies reporting encouraging data on diverse treatment strategies, including induction chemotherapy for functional preservation in larynx cancer, proton-beam therapy for advanced sinonasal malignancies, pretreatment PET scans to predict response to intensity-modulated radiotherapy (IMRT), and accelerated radiation treatment in combination with concurrent cisplatin for head and neck carcinomas. The symposium was sponsored by the American Society for Radiation Oncology, the American Head and Neck Society, the American Society of Clinical Oncology, and the Society of Nuclear Medicine. Induction Chemotherapy Results in Low Risk of Voice Dysfunction Gilles Calais, MD, a radiation oncologist at Hospital Bretonneau in Tours, France, presented findings of a study of induction chemotherapy followed by radiation therapy as a larynx-preserving treatment showing that patients who received the treatment and survived for five years with an intact, functional larynx had a low risk of severe voice disability, and almost 50% of patients had no eating or swallowing problems.MIN YAO, MD, PhD: “High SUV is a possible indicator of a more aggressive cancer and a worse outcome, which may indicate a need for more aggressive treatment. Most interesting is the fact that SUV-LN is positively associated with distant metastasis, so possibly these patients should have more aggressive systemic chemotherapy treatment.”Dr. Calais noted that although studies have shown that a combination of chemotherapy and radiation can achieve a cure rate similar to that of total laryngectomy while preserving the larynx in 75% to 80% of patients, those studies did not usually report how well the larynx and esophagus functioned afterward in terms of voice quality and ability to swallow. The researchers examined two groups of patients (total of 213) who received different induction chemotherapy regimens. One group of 110 patients received cisplatin and fluorouracil (5-FU) plus docetaxel (TPF); the other group of 103 patients received cisplatin and 5-FU, without docetaxel (PF). Radiation therapy was given to those who responded well to the initial chemotherapy; those who didn't had total laryngectomy followed by radiation. Clearly, the TPF regimen achieved better results, Dr. Calais reported. Among patients who survived five years after treatment, the larynx-preservation rates were 74% in those who received the TPF regimen and 51% among those who received the PF regimen. Using patient questionnaires, the team evaluated voice quality, nutritional function, and quality of life among the survivors (follow-up occurred at a median of 61 months from treatment). Averaged over the two patient groups, the five-year laryngoesophageal dysfunction-free survival rate was 28% (36% of those who received the TPF regimen and 21% of those who received the PF regimen). Voice disability was low in 57% of patients and severe in only 15%. Only 8% of patients required a feeding tube. Asked for his opinion for his article, Louis B. Harrison, MD, Clinical Director of Continuum Cancer Centers of New York and the Gerald J. Friedman Chairman of Radiation Oncology at Beth Israel Medical Center and St. Luke's–Roosevelt Hospitals and Co-director of the Institute for Head and Neck and Thyroid Cancer, said the study highlights how important it is when treating patients with head and neck cancer, to diligently study the functional outcome with respect to speech and swallowing. So much progress has now been made using better combinations of chemotherapy and radiation that organ preservation should be considered “a real success story” in cancer control, he said. “But that's not enough today, to just control the cancer. You've got to control the cancer and leave the patient optimally functional.” Both physicians said that despite advances in induction chemotherapy, radiation therapy will continue to be a critical component of functional preservation of the larynx. PBRT Encouraging for Sinonasal Cancers Annie W. Chan, MD, a radiation oncologist at Massachusetts General Hospital and Assistant Professor of Radiation Oncology at Harvard Medical School, reported on the long-term outcomes of proton beam radiation therapy in treating patients with rare and aggressive sinonasal cancers.ANNIE W. CHAN, MD, is now preparing for publication a study that examines treatment outcomes in patients who received proton beam radiation therapy and concurrent chemotherapyThese patients often present with locally advanced tumors that affect the base of the skull, the eyes, optic nerves, and the brain. Symptoms may include headache, loss of vision, facial swelling, and nosebleed. Because of the anatomical structures affected, said Dr. Chan, “conventional radiation therapy results in very poor local control and is associated with significant treatment-related toxicity.” She and her colleagues followed 99 patients newly diagnosed with sinonasal cancers and treated with proton beam therapy at Mass General between 1991 and 2003. Sixty-five percent of patients had T4b disease, with a variety of histological subtypes, including squamous cell carcinoma, esthesioneuroblastoma/neuroendicrine tumors, adenoid cystic carcinoma, sarcoma, and adenocarcinoma. Two-thirds of the patients had surgery before the proton beam treatment. The median dose to the primary tumor was approximately 70 Gy. Eighty-two percent of patients received twice-daily radiation. The local control rates at five and eight years after treatment were 87% and 83%, respectively—very encouraging when compared with the rates achieved in other studies, Dr. Chan said. No statistically significant differences in local control according to histological subtype, tumor stage, or surgery versus biopsy were found. “Proton beam radiation therapy, with its superior dose distribution, allows the delivery of higher doses of radiation to the tumor while sparing more of the healthy surrounding tissues,” she noted. Very few (2%) of the patients in her study received concurrent chemotherapy, which is now the standard of care for many cancers, including advanced sinus cancers. She explained in a telephone interview that the study reported on the long-term outcomes of treatments that occurred over a dozen years, ending in 2003, before the benefits of concurrent chemotherapy were well known; therefore, that treatment was not yet in common use. Now being prepared for publication, she said, is another study that examines treatment outcomes in patients who received proton beam therapy and concurrent chemotherapy. Dr. Chan has now received funding from the National Cancer Institute to conduct a prospective multi-institutional study comparing proton beam therapy with other treatment modalities for sinonasal cancers. Of particular interest for comparison is intensity-modulated radiation therapy (IMRT), she said. Dr. Harrison emphasized the need for a balanced approach to new and expensive technology: “As Dr. Chan's study shows, proton beam radiation therapy holds great promise, but the incremental benefit of protons over photons needs to be borne out in clinical trials. Whether or not there's an improvement over conventional IMRT or stereotactic radiation we don't yet know, and that's what we need to study.” Prognostic Significance of Pre-treatment SUVPHUC FELIX NGUYEN-TAN, MDCM, presented a multi-institutional randomized Phase III trial showing that for patients with advanced head and neck cancer, when combined with concurrent cisplatin, accelerated fractionation was comparable to standard fractionation.Min Yao, MD, PhD, of the Department of Radiation Oncology at University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, presented data demonstrating the prognostic utility of measuring fluorodeoxyglucose (FDG) uptake in head and neck squamous cell carcinomas prior to treatment with IMRT. (Tumor uptake of FDG, a glucose analog that is not metabolized by cancer cells, is measured by PET scan and expressed as a standardized uptake value (SUV). The greater the uptake of FDG, the higher the cancer cell's metabolism and, it is thought, the more aggressive the cancer.) In a retrospective study of 295 patients, Dr. Yao and colleagues examined 177 (137 men and 40 women; median age of 57) who had FDG PET scans before IMRT and whose maximal SUV in the primary tumor (SUV-P) and/or lymph nodes (SUV-LN) was known. Fifty-two patients were treated with IMRT after surgery (10 had concurrent chemotherapy); in 125 patients, IMRT was the definitive treatment (99 had concurrent chemotherapy). Most patients (157) had locally advanced (Stage III or IV) large tumors; most frequently, tumors were of the oropharynx (87 patients), oral cavity (32 patients), or larynx (also 32 patients). Patients were treated from December 1999 to January 2006 at a single treatment facility. Follow-up occurred at a median of 22.6 months (range of 1.0 to 75.4 months); among surviving patients, follow-up occurred at a median of about 29 months (range of 5.5 to 75.4 months). There was a median pre-treatment SUV-P of 10.65 (range of 2.6 to 48.2) and a median pre-treatment SUV-LN of 7.33 (range of 1.5 to 33.1). SUV-P was found to be significantly associated with disease-specific survival and overall survival, and strongly associated with disease-free survival. SUV-LN was significantly associated with distant metastasis (patients with higher SUV-LN have a significantly higher incidence of distant disease). “High SUV is a possible indicator of a more aggressive cancer and a worse outcome, which may indicate a need for more aggressive treatment,” Dr. Yao said in an interview. “Most interesting is the fact that SUV-LN is positively associated with distant metastasis, so possibly these patients should have more aggressive systemic chemotherapy treatment.” For example, among the 25 patients who had distant metastasis three years after treatment, the median SUV-LN was 10.8; among the 106 patients without distant metastasis, the median SUV-LN was 7.0. “The major point is that with IMRT, we see better local-regional control but more patients with distant metastasis, and high values of both SUV-P and SUV-LN are associated with poorer outcomes,” Dr. Yao said, concluding, therefore, that SUV-LN may be used to select patients for treatments such as induction chemotherapy. Commenting on the study, the President of the Society of Nuclear Medicine, Michael Graham, MD, PhD, Head of Nuclear Medicine at the University of Iowa, said, “By doing head imaging before the treatment, you not only gain all the information about the staging of the cancer, where the cancer is, how extensive, but also how metabolically active it is, and that can make a significant difference in how aggressively you want to treat the cancer. This is likely to make a real difference in the care of the patient.”Speaking of Dr. Nguyen-Tan's study, MICHAEL GRAHAM, MD, PHD, said that since the results were the same in both the standard treatment and the accelerated treatment, “you might say so what? But the accelerated treatment allows the patient to spend less time at the radiotherapy facility or traveling to get treated; it's less expensive because they get less chemotherapy and these modern chemotherapies are often quite expensive; and there's likely to be less toxicity to their bone marrow because they do get less chemotherapy—so it actually is a real step forward, it's not just more of the same.”Less Toxicity with Accelerated Fractionation Phuc Felix Nguyen-Tan, MDCM, Assistant Professor of Radiation Oncology at Centre Hospitalier de l'Université de Montréal (CHUM), Hôpital Notre-Dame, in Montreal, reported on a multi-institutional randomized Phase III trial that compared the efficacy and toxicity of accelerated vs standard fractionation combined with concurrent cisplatin therapy for locally advanced head and neck carcinomas. The principal investigator of the study (RTOG 0129), was K. Kian Ang, MD, of the University of Texas M. D. Anderson Cancer Center in Houston. From July 2002 through May 2005, the researchers analyzed 721 patients with Stages III or IV carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Half of the patients (360) received an accelerated course of radiation with two cycles of cisplatin (the experimental arm); the other half (361 patients) received the standard radiation therapy with three cycles of cisplatin. A comparison of the accelerated and standard treatment groups at a median follow-up of 4.8 years showed very similar results: overall survival rates were 59% and 56%, respectively; disease-free survival rates were 45% and 44%, respectively; local-regional failure rates were 31% and 28%, respectively; and distant metastasis rates were 18% and 22%, respectively.LOUIS B. HARRISON, MD: “So much progress has now been made using better combinations of chemotherapy and radiation that organ preservation should be considered a real success story in cancer control. But that's not enough today to just control the cancer. You've got to control the cancer and leave the patient optimally functional.”“The main point is that the experimental arm in this case yielded results that were similar to the standard treatment in terms of efficacy,” Dr. Nguyen-Tan explained in an interview. “The fact that the experimental treatment didn't yield inferior outcomes represents an advance, because we're giving only two cycles of chemotherapy and it exposes the patient to less chemotherapeutic toxicities.” Crucially, “the benefit of the third cisplatin cycle appeared minimal.” Dr. Graham said, “The observation was that the results were the same in both the standard treatment and the accelerated treatment—and you might say ‘Well, so what?’ The accelerated treatment allows the patient to spend less time at the radiotherapy facility or traveling to get treated; it's less expensive because they get less chemotherapy and these modern chemotherapies are often quite expensive; and there's likely to be less toxicity to their bone marrow because they do get less chemotherapy—so it actually is a real step forward, it's not just more of the same.”

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