Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The survival advantage of induction chemotherapy (IC) followed by locoregional treatment is controversial in locally advanced head and neck squamous cell carcinoma (LAHNSCC). We previously showed feasibility and safety of cetuximab-based IC (paclitaxel/carboplatin/cetuximab-PCC, and docetaxel/cisplatin/5-fluorouracil/cetuximab-C-TPF) followed by local therapy in LAHNSCC. The primary end point of this phase II clinical trial with randomization to PCC and C-TPF followed by combined local therapy in patients with LAHNSCC stratified by human papillomavirus (HPV) status and T-stage was 2-year progression-free survival (PFS) compared with historical control. PATIENTS AND METHODS: Eligible patients were ≥18 years with squamous cell carcinoma of the oropharynx, oral cavity, nasopharynx, hypopharynx, or larynx with measurable stage IV (T0-4N2b-2c/3M0) and known HPV by p16 status. Stratification was by HPV and T-stage into one of the two risk groups: (i) low-risk: HPV-positive and T0-3 or HPV-negative and T0-2; (ii) intermediate/high-risk: HPV-positive and T4 or HPV-negative and T3-4. Patient reported outcomes were carried out. RESULTS: A total of 136 patients were randomized in the study, 68 to each arm. With a median follow up of 3.2 years, the 2-year PFS in the PCC arm was 89% in the overall, 96% in the low-risk and 67% in the intermediate/high-risk groups; in the C-TPF arm 2-year PFS was 88% in the overall, 88% in the low-risk and 89% in the intermediate/high-risk groups. CONCLUSION: The observed 2-year PFS of PCC in the low-risk group and of C-TPF in the intermediate/high-risk group showed a 20% improvement compared with the historical control derived from RTOG-0129, therefore reaching the primary end point of the trial.

Interactive website for head and neck cancer patients: Adherence and coping program to prevent dysphagia after radiation.

INTRODUCTION: Pharyngeal and laryngeal cancers are highly curable; however survivors are at high risk for long-term dysphagia after radiation. To address lack of access to preventive care in community settings, we developed a responsive web-based application to help patients adhere to preventive swallowing exercises and cope with radiation side effects. We conducted an interim study analysis to determine website usage characteristics and to examine the effect size for future trials. METHODS: Pharyngeal and laryngeal cancer patients were recruited for enrollment by speech language pathologists before primary radiation and introduced to the interactive website. The program (English and Spanish) features tracking logs for preventive exercises, instructional videos, patient stories and search features. Patients' self-reported swallowing function was assessed with the MD Anderson Dysphagia Inventory (MDADI) at baseline and at 6 months. Adherence to preventive exercises was assessed during the 10 week intervention. Number of unique website visits, total duration of website exposure, and rankings of the most popular webpages were calculated. Preliminary regression models were run using adherence and MDADI as outcomes. RESULTS: Of the 160 enrolled, 96 had 10-week adherence data and 61 had 6-month MDADI data. The average age was 63 (SD = 12.26), 49.4% were from rural counties, 44% had a high school education or lower, and 42% reported annual income of $30,000 or less. The average number of visits was 5.49 (SD = 9.96) and the average total time spent with the website was 41.09 min (SD =88.48). Preliminary analyses indicated that number of unique visits to the website was independently associated with increased adherence to preventive exercises (p = .001-.008). CONCLUSION: Our website showed significant effects in promoting adherence to swallowing exercises. However, our return visit rate showed that the platform needs improvement in navigability and usability for this older population undergoing challenging treatment in community settings with low resources.

Expectations and experience of labial reduction: a qualitative study.

OBJECTIVE: To understand women's reasons for undergoing labial reduction surgery, their expectations and experiences. DESIGN: A retrospective qualitative study. SETTING: British National Health Service Hospital. SAMPLE: Six women who had experienced surgery for labial reduction. Method Qualitative study using semi-structured interviews. RESULTS: Results relating to 'Normality and defect', 'Sex lives' and 'The process of accessing surgery' are presented in this study. The women had seen their presurgery genital appearance as 'defective' and sought a 'normal' genital appearance. They thought that their presurgery genital appearance impacted on their sex lives, but their expectations of the effects of surgery on their sex lives were not all fulfilled. Information about labial surgery came from both the popular media and the health services. An emphasis on, for example, physical discomfort rather than appearance may have been used to legitimise a request for surgery. The process of accessing surgery had exposed them to potentially conflicting messages about their genital appearance. CONCLUSIONS: Women presenting for labial reduction may have unrealistic expectations of surgery, but their perceptions and expectations are long-standing and seem to be based on strong cultural norms. The gynaecologist is also meeting those women who have already negotiated the referral process. As demand for this surgery appears to be increasing, further research is needed. These findings may add to the case for the potential value of specialist staff to provide psychosocial interventions within gynaecology services.

Radiotherapy for head and neck cancer.

The length and quality of head and neck cancer survivorship continues to improve. Radiotherapy has been central to this process through advances in treatment technology, fractionation schemas, radiosensitizing chemotherapy, and surgical technique. The future of head and neck radiotherapy looks brighter still with progress in radiosensitizing biologic therapy, molecular characterization, functional imaging, and rehabilitative strategies fast approaching. Head and neck cancer, a disease once fraught with nihilism and failure, is evolving into a major success story of multidisciplinary solid tumor management. Continued dedication and work on the part of provider and patient alike will be required to make this promise a reality.

Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck.

PURPOSE: To define further the role of concurrent chemoradiotherapy for patients with advanced squamous carcinoma of the head and neck. PATIENTS AND METHODS: The Radiation Therapy Oncology Group developed this three-arm randomized phase II trial. Patients with stage III or IV squamous carcinoma of the oral cavity, oropharynx, or hypopharynx were eligible. Each of three arms proposed a radiation schedule of 70 Gy in 35 fractions. Patients on arm 1 were to receive cisplatin 10 mg/m(2) daily and fluorouracil (FU) 400 mg/m(2) continuous infusion (CI) daily for the final 10 days of treatment. Treatment on arm 2 consisted of hydroxyurea 1 g every 12 hours and FU 800 mg/m(2)/d CI delivered with each fraction of radiation. Arm 3 patients were to receive weekly paclitaxel 30 mg/m(2) and cisplatin 20 mg/m(2). Patients randomly assigned to arms 1 and 3 were to receive their treatments every week; patients on arm 2 were to receive their therapy every other week. RESULTS: Between 1997 and 1999, 241 patients were entered onto study; 231 were analyzable. Ninety-two percent, 79%, and 83% of patients on arms 1, 2, and 3, respectively, were able to complete their radiation as planned or with an acceptable variation. Fewer than 10% of patients had unacceptable deviations or incomplete chemotherapy in the three arms. Estimated 2-year disease-free and overall survival rates were 38.2% and 57.4% for arm 1, 48.6% and 69.4% for arm 2, and 51.3% and 66.6% for arm 3. CONCLUSION: We have demonstrated that three different approaches of concurrent multiagent chemotherapy and radiation were feasible and could be delivered to patients in a multi-institutional setting with high compliance rates.

Combined interferon-alfa, 13-cis-retinoic acid, and alpha-tocopherol in locally advanced head and neck squamous cell carcinoma: novel bioadjuvant phase II trial.

PURPOSE: Retinoids and interferons (IFNs) have single-agent and synergistic combined effects in modulating cell proliferation, differentiation, and apoptosis in vitro and clinical activity in vivo in the head and neck and other sites. Alpha-tocopherol has chemopreventive activity in the head and neck and may decrease 13-cis-retinoic acid (13-cRA) toxicity. We designed the present phase II adjuvant trial to prevent recurrence or second primary tumors (SPTs) using 13-cRA, IFN-alpha, and alpha-tocopherol in locally advanced-stage head and neck cancer. PATIENTS AND METHODS: After definitive local treatment with surgery, radiotherapy, or both, patients with locally advanced SCCHN were treated with 13-cRA (50 mg/m(2)/d, orally, daily), IFN-alpha (3 x 10(6) IU/m(2), subcutaneous injection, three times a week), and alpha-tocopherol (1,200 IU/d, orally, daily) for 12 months, with a dose modification. Screening for recurrence or SPTs was performed every 3 months. RESULTS: Tumors of 11 (24%) of the 45 treated patients were stage III, and 34 (76%) were stage IV. Thirty-eight (86%) of 44 patients completed the full 12-month treatment (doses modified as needed). Toxicity generally was consistent with previous IFN and 13-cRA reports and included mild to moderate mucocutaneous and flu-like symptoms; occasional significant fatigue (grade 3 in 7% of patients), mild to moderate hypertriglyceridemia in 30% of patients who continued treatment along with antilipid therapy, and mild hematologic side effects. Six patients did not complete the planned treatment because of intolerable toxicity or social problems. At a median 24-months of follow-up, our clinical end point rates were 9% for local/regional recurrence (four patients), 5% for local/regional recurrence and distant metastases (two patients), and 2% for SPT (one patient), which was acute promyelocytic leukemia (ie, not of the upper aerodigestive tract). Median 1- and 2-year rates of overall survival were 98% and 91%, respectively, and of disease-free survival were 91% and 84%, respectively. CONCLUSION: The novel biologic agent combination of IFN-alpha, 13-cRA, and alpha-tocopherol was generally well tolerated and promising as adjuvant therapy for locally advanced squamous cell carcinoma of the head and neck. We are currently conducting a phase III randomized study of this combination (v no treatment) to confirm these phase II study results.

Phase I/II trial of radiation with chemotherapy "boost" for advanced squamous cell carcinomas of the head and neck: toxicities and responses.

PURPOSE: Extrapolating from our experience delivering a "boost" field of radiation concurrently with fields treating both gross and subclinical disease at the end of a course of radiation therapy, we developed a regimen to deliver concurrent chemotherapy during the last 2 weeks of a conventionally fractionated course of radiation. PATIENTS AND METHODS: Patients had stage III or IV biopsy-proven squamous cell carcinoma originating from a head and neck mucosal site. The regimen was 70 Gy delivered over 7 weeks with concurrent fluorouracil (5-FU) and cisplatin given daily with each radiation dose during the last 2 weeks. A phase I study was performed to determine the maximum-tolerated dose (MTD) before a phase II study was conducted. RESULTS: The MTD was 400 mg/m(2) per day for 5-FU and 10 mg/m(2) per day for cisplatin. Mucositis persisting more than 6 weeks after therapy was the dose-limiting toxicity. A total of 60 patients were treated on the two phases of the study. Eighteen patients (35%) treated at the MTD developed prolonged mucositis. There were two cases of neutropenic sepsis, including one fatality. The actuarial 2-year rates for overall survival, freedom from relapse, and local control were 62%, 59%, and 80%, respectively. CONCLUSION: Preliminary locoregional control rates seem to be higher than those reported for treatment with radiation alone. Toxicity was also greater than that seen with radiation alone, but the regimen was designed to deliver an intense treatment schedule, which could be completed without significant interruptions, and to obtain high control rates above the clavicles. These end points were achieved.

The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation.

PURPOSE: Surgery is the primary treatment for adenoid cystic carcinomas arising from major and minor salivary glands of the head and neck. However, local recurrence is frequent because of the infiltrative growth pattern and perineural spread associated with these tumors. At UTMDACC, we have had a longstanding policy of using postoperative radiotherapy to reduce the risk of local recurrence and to avoid the need for radical surgery; this 30-year retrospective study analyzes the results of this combined modality approach. METHODS AND MATERIALS: Between 1962 and 1991, 198 patients ages 13-82 years, with adenoid cystic carcinomas of the head and neck, received postoperative radiotherapy for known or suspected microscopic residual disease following surgery. Distribution of primary sites was: parotid: 30 patients; submandibular/sublingual: 41 patients; lacrimal: 5 patients; and minor salivary glands: 122 patients. Eighty-three patients (42%) had microscopic positive margins and an additional 55 (28%) had close (< or = 5 mm) or uncertain margins. One hundred thirty-six patients (69%) had perineural spread with invasion of a major (named) nerve in 55 patients (28%). Using radiation techniques appropriate to the primary site, a median dose of 60 Gy (range 50-69 Gy) was delivered to the tumor bed. Follow-up ranged from 5-341 months (median, 93 months). All surviving patients had a minimum of 2 years follow-up. RESULTS: Twenty-three patients (12%) had local recurrences with 5-, 10-, and 15-year actuarial local control rates of 95%, 86%, and 79%, respectively. Fifteen of the 83 patients (18%) with positive margins developed local recurrences, compared to 5 of 55 patients (9%) with close or uncertain margins, and 3 of 60 patients (5%) with negative margins (p = 0.02). Patients with and without a major (named) nerve involved had crude failure rates of 18% (10 out of 55) and 9% (13 out of 143), respectively (p = 0.02). There was a trend toward better local control with increasing dose. This was significant in patients with positive margins, in whom crude control rates were 40 and 88% for doses of < 56 Gy and > or = 56 Gy, respectively (p = 0.006). Actuarial 5-, 10-, and 15-year freedom from relapse rates were 68%, 52%, and 45%, respectively. Base of skull and neck failures were uncommon with or without elective treatment, developing in 2 and 3% of patients, respectively. Distant metastases were the most common type of disease recurrence, developing in 74 patients (37%) of whom 62 (31%) were disease-free at the primary site. CONCLUSIONS: Excellent local control rates were obtained in this population using surgery and postoperative radiotherapy and we recommend this combined approach for most patients with adenoid cystic carcinomas of the head and neck. Perineural invasion was an adverse prognostic factor only when a major (named) nerve was involved. Microscopic positive margins was also an adverse prognostic factor, but even when present, local control was achieved in over 80% of our patients. We recommend a dose of 60 Gy to the tumor bed, supplemented to 66 Gy for patients with positive margins. Despite effective local therapy, one-third of patients fail systemically, and good treatment to address this problem is lacking.

Hyperfractionated radiation in the treatment of squamous cell carcinomas of the head and neck: a comparison of two fractionation schedules.

PURPOSE: In 1984 we began treating patients with squamous cell carcinomas of the larynx and hypopharynx with hyperfractionated radiotherapy. Patients received 76.8 Gy in 1.2 Gy fractions twice daily, with a 4 h interfraction interval. In 1988, this schedule was modified in patients treated with shrinking field techniques. The dose per fraction was slightly reduced (while not changing the total dose), and the interfraction interval was increased to 6 h. The goal was to decrease toxicity while maintaining satisfactory local-regional control. This retrospective study analyzes the results of this schedule modification. METHODS AND MATERIALS: Two hundred thirty-six patients were included in the analysis. Distribution of patients by primary site and T stage was as follows: supraglottic larynx, 120 patients; hypopharynx, 70; true vocal cord, 24; and oropharynx, 22; T1, 5 patients; T2, 118; T3, 93; T4, 19; and Tx, 1. Ninety-nine patients presented with cervical nodal disease. Seventy-eight patients (group A), including 16 treated with induction chemotherapy, were treated throughout with 1.2 Gy fractions twice daily and a 4-h interfraction interval. Subsequently, 158 patients (group B), 57 of whom received chemotherapy, received 1.1 Gy fractions to 55 Gy, and then 1.2 Gy fractions to their boost volumes to 76.6 Gy. The interfraction interval was 6 h. Median follow-up was 91 and 35 months for group A and B, respectively. RESULTS: Two-year actuarial survival, local control, and ultimate local rates were 70%, 75%, and 85%, respectively. Differences between survival rates for group A and group B were not statistically significant, with 2-year rates of 66% and 72%, respectively. Overall local control rates at 2 years were 77% and 74%, respectively, for groups A and B (p = 0.22). However, there was a trend toward inferior results in group B patients with T3 disease (67% at 2 years compared to 76% in group A, p = 0.13). Confluent mucositis and persistent mucositis developed in 52% and 14% of group A patients, but only 37% and 4% of group B patients (p = 0.02 and p < 0.01, respectively). There was a near significant trend toward fewer late complications in group B who developed an 8% complication rate at 3 years compared to 15% of group A patients (p = 0.07). CONCLUSIONS: The net effect of reducing the dose per fraction to 1.1 Gy twice daily for fields covering gross disease and subclinical sites, and increasing the interfraction interval to 6 h was to reduce the incidence of both acute and late complications. Excellent overall local control rates (85%) for T2 lesions were achieved with both hyperfractionation regimens and we, therefore, continue to treat patients with T2 tumors with the modified schedule. The overall results in selected patients with T3 lesions was also satisfactory (69%), but as there was a trend towards poorer local control in patients treated with 1.1 Gy fractions, we recommend using 1.2 Gy for the entire treatment of these patients, while maintaining the 6 h interfraction interval to reduce the risk of late complications.

Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of local and regional control.

PURPOSE: This retrospective study was conducted to review the results of treatment and to identify prognostic factors for local and regional control in a population of 378 patients with nasopharyngeal carcinomas treated in a single institution by radiation therapy alone. METHODS AND MATERIAL: All patients were treated at The University of Texas M. D. Anderson Cancer Center between 1954 and 1992 following a consistent treatment philosophy but with evolving technique. There were 286 males and 92 females with a median age of 52 years (range: 16-86 years). The majority of the patients were Caucasian (282 patients, 75%). Thirty-two patients (8%) had one or more cranial nerve deficits. Three-fourths of the patients presented with AJCC Stage IV disease (T4, N0-3, 118 patients; T1-3, N2-3 164 patients). Histologically, 193 tumors (51%) were squamous cell carcinomas, 154 (41%) lymphoepitheliomas, and 31 (8%) unclassified carcinomas. Average total dose varied with T-stage and ranged from 60.2 to 72.0 Gy. Median follow-up time was 10 years. RESULTS: For the entire population the 5-, 10-, and 20-year actuarial survival rates were 48, 34, and 18%, respectively, with 184 patients (49%) dying of nasopharyngeal cancer. Actuarial control rates at 5, 10, and 20 years were 71, 66, and 66% for the primary site and 84, 83, and 83% for the neck. A total of 100 patients (26%) had local failures and 51 patients (13%) had regional failures with a median time to recurrence of 8.2 months and 13 months, respectively. Advanced T-stage, squamous histology, and presence of cranial nerve deficits were poor prognostic factors for local control in both univariate and multivariate analyses. N-stage and tumor histology were significant factors for neck control. Treatment year, total dose within the ranges used, and duration of treatment did not have any significant effect on local or regional control. The actuarial incidence of Grade 3-5 late complications was 16, 19, and 29% at 5, 10, and 20 years, respectively. Twelve patients (3%) died of treatment-related complications; all but one fatal complication occurred before 1971 and the other in 1976. CONCLUSIONS: This study shows very good long-term local and regional control rates for nasopharyngeal carcinomas after definitive radiotherapy and establishes a benchmark for newer treatment strategies. Improvements in treatment technique over the years have dramatically reduced the frequency of severe late complications. Patients with advanced stage tumors and differentiated squamous histology have a relatively poor prognosis when treated with conventional radiotherapy and are candidates for dose escalation or combined modality studies.

Base-of-tongue carcinoma: treatment results using concomitant boost radiotherapy.

PURPOSE: To evaluate the efficacy of accelerated fractionated radiotherapy using the concomitant boost schedule for patients with squamous cell carcinoma of the base of tongue. METHODS AND MATERIALS: Between September 1984 and July 1992, 54 patients with squamous carcinoma of the base of tongue were treated at The University of Texas M. D. Anderson Cancer Center using the concomitant boost schedule. The distribution of T and N stages was T1-4, T2-27, T3-22, and T4-1; N0-9, N1-11, N2-24, N3-7, and NX-3. American Joint Committee on Cancer (AJCC) stage groupings were II-6, III-14, and IV-34. Before radiation, nodal excision and neck dissection were done in 5 and 10 patients, respectively; 5 patients had neck dissections after radiotherapy. Standard on and off spinal cord fields were irradiated with 1.8 Gy fractions to 54 Gy given over 6 weeks. The boost was given concomitantly during the large field treatment as a second daily (1.5 Gy) fraction, with an interfraction interval of 4-6 h. The median dose to the primary tumor was 72 Gy (range, 66-74 Gy). The median treatment duration was 42 days (range, 39-48 days). Only three patients had treatment interrupted for more than one scheduled treatment day. RESULTS: The 5-year actuarial overall survival and disease-specific survival rates were 59 and 65%, respectively, with a median follow-up of 41 months. The 5-year actuarial locoregional control rate was 76%. The actuarial local control rates achieved with radiotherapy at 5 years for T1, T2, and T3 primary tumors were 100%, 96%, and 67%, respectively; including surgical salvage, the local control rate of T3 primary tumors was 70%. Six patients had regional failures, which in three patients occurred in conjunction with primary tumor recurrence. Twenty-six patients with regional adenopathy were treated with radiation alone to full dose and had a complete clinical response in the neck; no planned neck dissections were performed in these patients. Only 2 of these 26 patients had subsequent regional failures. The 5-year actuarial risk of distant metastases in patients whose disease was controlled locoregionally was 21%. Grade 3 or 4 confluent acute mucositis occurred in 94% of patients. However, late complications were limited to two cases of transient mandibular exposure and three cases of self-limited mucosal ulcerations. CONCLUSION: The concomitant boost fractionation schedule is a very effective regimen for this disease when appropriately selected patients are treated with meticulous technique. The therapeutic ratio is favorable, with a high rate of disease control and no persistent severe late complications. Patients whose neck disease responds completely to treatment with this schedule do not appear to need a planned neck dissection.

Water bolus for electron irradiation of the ear canal.

PURPOSE: To demonstrate that water bolus in the external ear can decrease the dose inhomogeneity caused by auricular surface irregularities when the ear is in an electron-beam field. METHODS AND MATERIALS: Three-dimensional (3D) dose distributions with and without water bolus in the external ear were calculated for a representative patient. The electron dose calculations were made using the Hogstrom pencil beam algorithm as implemented in 3D by Starkschall. To demonstrate the use of water bolus in the ear clinically, the case of a patient with squamous carcinoma of the concha who was treated with electrons is presented. RESULTS: Water bolus markedly lessens the dose heterogeneity caused by the surface irregularities of the ear and the air in the external auditory canal. In the test case, the maximum dose was reduced by 25% using this technique. CONCLUSION: When the ear is in an electron beam field, warm water should be placed in the external auditory canal and concha. This maneuver may reduce the incidence of auricular complications that occur after electron-beam therapy.

Does induction chemotherapy have a role in the management of nasopharyngeal carcinoma? Results of treatment in the era of computerized tomography.

PURPOSE: To assess the outcomes of patients with nasopharyngeal carcinoma (NPC) whose treatment was determined by computerized tomography (CT) and/or magnetic resonance imaging staging and to analyze the impact of induction chemotherapy and accelerated fractionated radiotherapy. METHODS AND MATERIALS: The analysis is based on 122 of 143 previously untreated patients with NPC treated with radiation therapy at The University of Texas M. D. Anderson Cancer Center between 1983 and 1992. Excluded were 4 patients treated with palliative intent, 4 children, 12 patients not staged with CT, and 1 patient who died of a cerebrovascular accident prior to completion of treatment. The stage distribution was as follows: AJCC Stage I-2, Stage II-7, Stage III-12, Stage IV-101; Tl-15, T2-33, T3-22, T4-52; N0-32, N1-10, N2-47, N3-32, Nx-1. Fifty-nine (48%) patients had squamous cell carcinoma; 63 (52%) had lymphoepitheliomas, undifferentiated NPC or poorly differentiated carcinoma, NOS (UNPC). Sixty-seven patients (65 with Stage IV disease) received induction chemotherapy. Fifty-eight patients (24 of whom had induction chemotherapy) were treated with the concomitant boost fractionation schedule. The median follow-up for surviving patients was 57 months. RESULTS: The overall actuarial 2- and 5-year survival rates were 78 and 68%, respectively. Forty-nine patients (40%) had disease recurrence. Thirty-three (27%) had local regional failures; 19 at the primary site only, 8 in the neck and 6 in both. Local failure occurred in 31% of patients staged T4 compared to 13% of T1-T3 (p = 0.007). Sixteen patients failed at distant sites alone. Among Stage IV patients the 5-year actuarial rates for patients who did and did not receive induction chemotherapy were as follows: overall survival: 68 vs. 56% (p = 0.02), freedom from relapse: 64 vs. 37% (p = 0.01), and local control: 86 vs. 56% (p = 0.009). The actuarial 5-year distant failure rate in patients with UNPC who were treated with induction chemotherapy and controlled in the primary and neck was 13%. In patients who did not receive chemotherapy, the actuarial 5-year local control rates for patients treated with concomitant boost or conventional fractionation were 66 and 67%, respectively. CONCLUSIONS: While not providing conclusive evidence, this single institution experience suggests that neoadjuvant chemotherapy for Stage IV NPC patients improves both survival and disease control. Recurrence within the irradiated volume was the most prevalent mode of failure and future studies will evaluate regimens to enhance local regional control.

Comparison between normal tissue reactions and local tumor control in head and neck cancer patients treated by definitive radiotherapy.

PURPOSE: This study was conducted to test for the relationship between tumor and normal tissue radiosensitivity, by comparing local tumor control to the severity of acute and late normal tissue reactions in head and neck cancer patients treated by definitive radiotherapy. METHODS AND MATERIALS: Two hundred eighty-six patients with head and neck cancer who were treated at the University of Texas M. D. Anderson Cancer Center between 1983 and 1993 were selected for the study. Of these, 124 (43%) were treated by a concomitant boost regimen and 162 (57%) by hyperfractionation. All patients had at least 1 year of follow-up. The tumor stage distribution according to the 1992 American Joint Committee on Cancer (AJCC) staging system was as follows: T1, 3%; T2, 53%; T3, 40%; T4, 4%. The average doses delivered were 71.2 Gy and 76.2 Gy for the concomitant boost and hyperfractionation regimens, respectively, with no significant variation between patients. Acute and late reactions were recorded using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research on Treatment of Cancer (EORTC) grading system (0 to 4). The median follow-up period was 38 months (range: 12-107 months). The time to local tumor recurrence was analyzed in relation to the severity of acute and late reactions expressed as the maximum recorded grades, and to the time intensity of acute mucositis, expressed as the area under the curve of mucositis grade vs. time. Univariate and multivariate analyses also included T stage, N stage, and site of origin as other prognostic variables, and were carried out using a proportional hazards model. RESULTS: Fifty-four patients (19%) suffered local failure. T stage was found to significantly influence local control (p = 0.009). There was a nonsignificant trend for higher failure rates in patients with maximum Grade 1 or 2 vs. those with Grade 3 or 4 acute mucositis (28 and 18%, respectively; p = 0.17). No correlation was found between the severity of late reactions and local tumor control after radiotherapy. Analysis by time intensity of mucositis revealed a wide variation between individuals with a nonsignificant trend for higher local failure rates in patients with low mucositis time intensity scores. CONCLUSIONS: These clinical results suggest a possible relationship between normal tissue and tumor radiosensitivity. However, additional studies with a larger numbers of patients, and using refined normal tissue endpoints that incorporate a time function are needed to fully elucidate this question.

Postoperative radiotherapy for malignant tumors of the parotid gland.

PURPOSE: To update our experience using postoperative irradiation in selected patients with carcinomas of the parotid gland. Outcomes of treatment with a focus on the effectiveness of the two primary techniques of radiation used for treating these tumors were evaluated. METHODS AND MATERIALS: A retrospective analysis of 166 patients with parotid gland malignancies treated in the Department of Radiotherapy at the University of Texas M. D. Anderson Cancer Center between 1965-1989 was performed. All patients were treated following surgery and did not have macroscopic disease at the time of their radiation. The most common histologies were mucoepidermoid carcinoma (28%) and adenocarcinoma (27%). Pathologic features constituting indications for postoperative radiotherapy included: inadequate margins, 104 (63%) cases; extraglandular disease extension, 82 (49%); perineural invasion 57 (34%); and nodal disease 43 (26%). Radiation was delivered through an ipsilateral field of predominantly high energy electrons in 142 patients (86%). Wedged paired 60Co fields were used to treat 19 patients. The median dose was 60 Gy, typically delivered at 2 Gy per fraction. The median follow-up time for surviving patients was 155 months. RESULTS: Forty-seven (29%) patients had disease recurrence, of whom 15 (9%) had disease recur locally and 10 (6%) regionally (neck). There was no association between the dose of radiation and local failure, except for a trend for patients with positive margins and/or named nerve involvement to have improved local control if they received doses > 60 Gy. There was no difference in failure rates in patients treated with wedged pair techniques or ipsilateral fields, but there was a higher complication rate in the former. Overall, 37 patients (22%) developed chronic sequelae attributed to radiation. Twelve patients developed decreased hearing, and 15 patients developed soft tissue or bone necrosis or exposure. CONCLUSIONS: Local and regional control rates for high risk patients with parotid gland carcinomas treated with radiation following surgery were excellent. The technique of using an ipsilateral field encompassing the parotid bed and treated with high energy electrons often mixed with photons was effective with minimal severe late toxicity. The moderate complication rate experienced in this series can be further reduced using modern techniques as described.

Superior sulcus tumors: treatment selection and results for 85 patients without metastasis (Mo) at presentation.

Superior sulcus (Pancoast) tumors (SST) are uncommon carcinomas of the lung with distinctive failure patterns and a somewhat more favorable prognosis than other sites of lung cancer. The most effective use of surgery (S), radiation (R), and chemotherapy (C) is not resolved. Most reported series include patients treated before the era of computed tomography (CT). A retrospective study was undertaken of all previously untreated patients with SST who received definitive management at the University of Texas M.D. Anderson Cancer Center between January 1977 and December 1987. Eighty-five patients were treated: the male:female ratio was 2.7:1, and the ages ranged from 35 to 80 (median 59) years. Karnofsky performance status (KPS) was 80 or more in 70 patients (82%). Thirty patients (35%) had lost 5% or more body weight. All had histologic or cytologic confirmation of carcinoma: 25% were squamous cell, 2% small cell, 54% adenocarcinoma, and 6% were large cell carcinoma (12% were not classified). After complete evaluation, 43 were classified as clinical Stage IIIA and 42 were Stage IIIB. One Stage IIIA patient received surgery, 13 surgery + radiation therapy, 2 surgery + radiation therapy and chemotherapy, 19 radiation therapy and 8 radiation therapy + chemotherapy. Seven Stage IIIB patients received surgery + radiation therapy, 12 radiation therapy, 2 surgery + radiation therapy + chemotherapy, 17 radiation therapy + chemotherapy and 4 chemotherapy. Surgery was a component of therapy more frequently in Stage IIIA than IIIB (p less than .05) and systemic treatment chemotherapy was used significantly more often (p less than .01) in Stage IIIB. Twenty-six patients (31%) lived 2 years or more (25+ to 131+ months) after treatment. Stage IIIA patients had a 46.5% 2-year survival rate compared to 20.6% for Stage IIIB (p = .0042). The one patient treated with surgery alone lived 2 years; 23% (7/31) of patients who had radiation therapy alone and none of the 4 who had chemotherapy lived 2 years. When surgery was a component of treatment, 52% (13/25) lived 2+ years, compared with 22% (13/60) when surgery was not part of treatment. When radiation therapy was part of treatment 31% lived 2 years and when chemotherapy was used, 18% lived 2 years. Fifty-two patients (61%) had control of the local tumor: their survival was significantly greater (p less than .01) than those who had local failure.(ABSTRACT TRUNCATED AT 400 WORDS)

Concomitant boost radiotherapy for squamous carcinoma of the tonsillar fossa.

PURPOSE: To assess the efficacy of a concomitant boost fractionation schedule of radiotherapy for treating patients with squamous carcinoma of the tonsillar fossa. PATIENTS AND METHODS: Between December 1983 and November 1992, 83 patients with squamous carcinoma of the tonsil were treated with concomitant boost fractionation. The distribution of American Joint Committee on Cancer T stages was TX-4, T1-5, T2-29, T3-41, T4-4; N stages were NX-1, N0-26, N1-13, N2-31, N3-12. Patients were treated with standard large fields to 54 Gy in 6 weeks. The boost treatment consisted of a second daily 1.5 Gy fraction for 10-12 fractions, usually delivered during the final phase of treatment. The tumor dose was 69-72 Gy, given over 6 weeks. Twenty-one patients, who all had N2 or N3 regional disease, underwent neck dissections, either before (13 patients) or 6 weeks after radiotherapy (8 patients); the other patients were treated with radiotherapy alone. RESULTS: The 5-year actuarial disease-specific survival and overall survival rates were 71 and 60%, respectively. Patients with T2 and T3 primary tumors had 5-year actuarial local control rates of 96 and 78%, respectively. Patients with T3 disease who received the final-phase boost had a 5-year actuarial local control rate of 82%. Actuarial 5-year regional disease control rates were N0, 92%; N1, 76%; N2, 89%; and N3, 89%. The 21 patients who had neck dissections all had their disease regionally controlled. Patients presenting with nodal disease or after a node excision who were treated with radiation alone had a 5-year actuarial regional disease control rate of 79%. All but five patients had confluent Grade 4 mucositis during treatment. Severe late complications attributable to radiation included mandibular necrosis [1], in-field osteosarcoma [1], and chronic dysphagia for solid foods [5]. CONCLUSIONS: High rates of local and regional disease control were achieved with the concomitant boost fractionation schedule, with few cases of severe late morbidity. Patients with N2 and N3 neck disease were effectively treated with radiation and the selective use of neck dissections. The concomitant boost schedule is our preferred fractionation approach for treating patients with intermediate stage tonsil cancer who are not participating in our current research protocols.

Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation.

PURPOSE: Cognitive deficits after treatment for small cell lung cancer (SCLC) have been attributed to prophylactic cranial irradiation (PCI). A prospective study of neuropsychological function was undertaken to document the evolution and magnitude of neuropsychologic deficits. METHODS AND MATERIALS: Thirty patients with limited stage SCLC who responded well (29 complete response (CR), 1 partial response (PR)) to combination chemotherapy plus thoracic irradiation or resection were studied with neuropsychological tests in the cognitive domains of intelligence, frontal lobe function, language, memory, visual-perception, and motor dexterity prior to a planned course of PCI. Nine patients had a neurologic history that could influence testing. RESULTS: An unexpected 97% (29 out 30) of patients had evidence of cognitive dysfunction prior to PCI. The most frequent impairment was verbal memory, followed by frontal lobe dysfunction, and fine motor incoordination. Of the patients with no prior neurologic or substance abuse history, 20 out of 21 (95%) had impairments on neuropsychological assessment. This neurologically normal group was just as impaired as the group with such a history with respect to delayed verbal memory and frontal lobe executive function. Eleven patients had neuropsychological testing 6 to 20 months after PCI; no significant differences were found from their pretreatment tests. CONCLUSIONS: A high proportion of neurologically normal patients was limited SCLC and favorable responses to combination chemotherapy have specific cognitive deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI have shown no significant deterioration.

Postoperative radiotherapy for malignant tumors of the submandibular gland.

PURPOSE: This retrospective study assessed the outcome and patterns of failure for patients with malignant submandibular tumors treated with surgery and postoperative radiation. METHODS AND MATERIALS: Between 1965 and 1995, 83 patients aged 11-83 years old received postoperative radiotherapy after resection of submandibular gland carcinomas. The most common radiation technique was an appositional field to the submandibular gland bed using electrons either alone or mixed with photons. Primary tumor bed doses ranged from 50 to 69 Gy (median, 60 Gy). Regional lymph nodes (ipsilateral Levels I-IV) were irradiated in 66 patients to a median dose of 50 Gy. Follow-up time ranged from 5 to 321 months (median, 82 months). RESULTS: Actuarial locoregional control rates were 90%, 88%, and 88% at 2, 5, and 10 years, respectively. The corresponding disease-free survival rates were 76%, 60%, and 53%, because 27 of 74 patients (36%) who attained locoregional control developed distant metastases. Adenocarcinoma, high-grade histology, and treatment during the earlier years of the study were associated with worse locoregional control and disease-free survival. The median survival times for patients with and without locoregional control were 183 months and 19 months, respectively. Actuarial 2-, 5-, and 10-year survival rates were 84%, 71%, and 55%, respectively. Late complications occurred in 8 patients (osteoradionecrosis, 5 patients). CONCLUSIONS: High-risk cancers of the submandibular gland have a historic control rate of approximately 50% when treated with surgery alone. In the current series, locoregional control rates for high-risk patients with submandibular gland cancers treated with surgery and postoperative radiotherapy were excellent, with an actuarial locoregional control rate of 88% at 10 years.

Can positron emission tomography improve the quality of care for head-and-neck cancer patients?

PURPOSE: Fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) is a functional imaging modality that measures the relative uptake of 18FDG with PET. The purpose of this review is to assess the potential contribution of FDG-PET scans to the treatment of head-and-neck cancer patients. METHODS AND MATERIALS: Data were assessed from the literature with attention to what additional information may be gained from the use of FDG-PET in four clinical settings: (1) detection of occult metastatic disease in the neck, (2) detection of occult primaries in patients with neck metastases, (3) detection of synchronous primaries or metastatic disease in the chest, and (4) detection of residual/recurrent locoregional disease. RESULTS: Although the data are somewhat conflicting, FDG-PET appears to add little additional value to the physical examination and conventional imaging studies (supplemented by biopsy when appropriate) for the detection of subclinical nodal metastases, unknown primaries, or disease in the chest. However, FDG-PET scans are quite useful in differentiating residual/recurrent disease from treatment-induced normal tissue changes. A positive FDG-PET scan at 1 month after radiotherapy is highly indicative of the presence of residual disease, and a negative scan at 4 months after treatment is highly predictive of tumor eradication. CONCLUSIONS: Large-scale studies using newer generation equipment and more defined methods are needed to more rigorously assess the potential of FDG-PET in the detection of subclinical primary or simultaneous secondary tumors and of nodal or systemic spread. Currently, however, FDG-PET can contribute to the detection of residual/early recurrent tumors, leading to the timely institution of salvage therapy or the prevention of unnecessary biopsies of irradiated tissues, which may aggravate injury.