Causes of death among cancer patients.

Background: The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. Patients and methods: US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. Results: The greatest relative decrease in index-cancer death (generally from > 60% to < 30%) was among those with cancers of the testis, kidney, bladder, endometrium, breast, cervix, prostate, ovary, anus, colorectum, melanoma, and lymphoma. Index-cancer deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among <50-year olds (e.g. SMR >1,000 for lymphomas, P < 0.001). The highest SMRs were typically within the first year after cancer diagnosis (SMRs 10-10,000, P < 0.001). Prostate cancer patients had increasing SMRs from Alzheimer's disease, as did testicular patients from suicide. Conclusion: The risk of death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis.

Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx.

OBJECTIVE: The rapid worldwide rise in incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies confirming this disease as an entity distinct from traditional OPSCC. Based on pathology, surgical studies have revealed prognosticators specific to HPV-positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)-classification do not differentiate for survival, demonstrating the need for new, HPV-specific OPSCC staging. The objective of this study was to define a pathologic staging system specific to HPV-positive OPSCC. METHODS: Data were assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0) of 704 patients from five cancer centers. Analysis was performed for (a) the AJCC/UICC pathologic staging, (b) newly published clinical staging for non-surgically managed HPV-positive OPSCC, and (c) a novel, pathology-based, "HPVpath" staging system that combines features of the primary tumor and nodal metastases. RESULTS: A combination of AJCC/UICC pT-classification and pathology-confirmed metastatic node count (⩽4 versus ⩾5) yielded three groups: stages I (pT1-T2, ⩽4 nodes), II (pT1-T2, ⩾5 nodes; pT3-T4, ⩽4 nodes), and III (pT3-T4, ⩾5 nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%, 84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked prognostic definition. Newly published HPV-specific clinical stagings from non-surgically managed patients, although prognostic, showed lower precision for this surgically managed cohort. CONCLUSIONS: Three loco-regional "HPVpath" stages are identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary tumor pT-classification and metastatic node count. A workable, pathologic staging system is feasible to establish prognosis and guide adjuvant therapy decisions in surgically-managed HPV-positive OPSCC.

Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303).

BACKGROUND: E2303 evaluated cetuximab, paclitaxel, and carboplatin used as induction therapy and concomitant with radiation therapy in patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) determining pathologic complete response (CR), event-free survival (EFS), and toxicity. PATIENTS AND METHODS: Patients with resectable stage III/IV HNSCC underwent induction therapy with planned primary site restaging biopsies (at week 8 in clinical complete responders and at week 14 if disease persisted). Chemoradiation (CRT) began week 9. If week 14 biopsy was negative, patients completed CRT (68-72 Gy); otherwise, resection was carried out. p16 protein expression status was correlated with response/survival. RESULTS: Seventy-four patients were enrolled; 63 were eligible. Forty-four (70%) were free of surgery to the primary site, progression, and death 1-year post-treatment. Following induction, 41 (23 CR) underwent week 8 primary site biopsy and 24 (59%) had no tumor (pathologic CR). Week 14 biopsy during chemoradiation (50 Gy) in 34 (15 previously positive biopsy; 19 no prior biopsy) was negative in 33. Thus 90% of eligible patients completed CRT. Overall survival and EFS were 78% and 55% at 3 years, respectively. Disease progression in 23 patients (37%) was local only in 10 (16%), regional in 5 (8%), local and regional in 2 (3%), and distant in 5 patients (8%). There were no treatment-related deaths. Toxicity was primarily hematologic or radiation-related. p16 AQUA score was not associated with response/survival. CONCLUSIONS: Induction cetuximab, paclitaxel, and carboplatin followed by the same drug CRT is safe and induces high primary site response and promising survival. CLINICAL TRIALS NUMBER: NCT 00089297.

PET CT imaging in patients undergoing sentinel node biopsy for melanoma.

AIMS: Sentinel lymph node biopsy (SLNB) has been adopted in the surgical treatment of melanoma to reduce morbidity and enhance staging. Positron emission tomography with computerised tomography (PET/CT) has been utilised in the staging of patients with malignancy though the role of this imaging modality in early stage melanoma is unclear. This study examined the preoperative value of PET/CT in patients undergoing SLNB for malignant melanoma. METHODS: Patients presenting with primary melanoma without evidence of either locoregional or systemic metastasis were considered candidates for SLNB. Selected patients underwent preoperative PET/CT followed by definitive surgical therapy including SLNB with regional lymphadenectomy, where indicated. RESULTS: During a 12-month period 83 patients were identified as having undergone SLNB for melanoma, of which 37 (45%) had preoperative PET/CT. Mean melanoma thickness 1.9 mm and 2.4 mm (PET/CT vs. no PET/CT, p>0.05). 13 (15.6%) patients were found to have lymphatic metastasis at SLNB; nine of these patients underwent PET/CT, only two of these scans were suggestive of lymphatic metastasis (positive predictive value 24%, negative predictive value 76%). PET/CT revealed no unheralded metastatic disease but did identify a second occult malignancy in 4 (10.8%) patients undergoing therapy for melanoma. CONCLUSIONS: The results of this study do not support the use of PET/CT in patients undergoing SLNB for melanoma. SLNB appears to be a more sensitive staging modality in the detection of lymphatic metastasis; however PET/CT may have a future role as a screening tool for malignancy.

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.

Gastrostomy-site tumor recurrence is not always fatal.

Percutaneous gastrostomy (PEG) site tumor seeding is a rare occurrence with fewer than 30 reported cases. Reported treatment ranges from observation to wide excision with unanimously poor outcome. We report the first published case of a long-term survivor after resection of a PEG site recurrence and review our treatment approach.

Elevated furin expression in aggressive human head and neck tumors and tumor cell lines.

Pro-protein convertases (PCs) are proteases that recognize and cleave precursor proteins. Furin, a well-studied PC, is ubiquitously expressed, and it has been implicated in many physiological and pathological processes. Some substrates for furin, such as membrane type 1 (MT1) matrix metalloproteinase (MMP), an MMP that activates gelatinase, a collagen-degrading enzyme, are associated with the advanced malignant phenotype. This report examines the expression of furin in carcinoma cell lines of different invasive ability. The levels of furin mRNA and protein correlated with the aggressiveness of tumor cell lines derived from head and neck and lung cancers. Furin expression also was investigated in primary head and neck squamous cell carcinomas (HNSCCs). Furin mRNA was not detected in nonmetastasizing carcinomas. In contrast, furin mRNA was expressed in metastasizing HNSCCs. Immunohistochemistry and Western blot analysis confirmed these results at the protein level. Furin activity was investigated indirectly by evaluating the expression of the pro-form and the processed form of MT1-MMP. Metastasizing HNSCCs showed increased expression of MT1-MMP. Furthermore, pro-MT1-MMP expression was noted in most of the nonmetastasizing HNSCCs analyzed by Western blot, and it was absent in the metastasizing HNSCCs. This finding suggests a lower level of furin-mediated MT1-MMP activation in the less aggressive cancers. These observations indicate that furin plays a role in tumor progression. Its overexpression in more aggressive or metastasizing cancers resulted in increased MMP processing.

Image cytometry of cyclin D1: a prognostic marker for head and neck squamous cell carcinomas.

CCND1 gene amplification and cyclin D1 protein overexpression are indicators for poor prognosis in invasive head and neck carcinomas. Increased CCND1 gene dosage is a more sensitive prognostic factor than protein overexpression as evaluated by conventional immunohistochemical techniques. Qualitative immunohistochemistry cannot distinguish cyclin D1 overexpression accompanied by amplification of the CCND1 gene from overexpression associated with normal CCND1 gene copy number. To improve the sensitivity of cyclin D1 protein determination, we applied quantitative techniques of image analysis to evaluate cyclin D1 in 54 head and neck carcinomas. There was a significantly higher rate of occurrence of adverse events (P = 0.043) among patients with CCND1 gene amplification than among those without gene amplification. There was a strong association between CCND1 gene amplification (as detected by Southern blot analysis) and the highest nuclear score (by image cytometry of the immunostained tumor sections). The predominance of cells in the lowest nuclear score category was significantly associated with normal copy number (P = 0.005). Conversely, the highest nuclear score was a significant predictor of gene dosage (P = 0.02). Similarly, high nuclear score was a good predictor of death as the final outcome of the disease (P = 0.01). Although somewhat less accurate than Southern blotting, image cytometry of immunohistochemical cyclin D1 stain appears to be a promising tool that could be useful for other tumor marker expression studies.

Incidental parathyroidectomy during thyroid surgery does not cause transient symptomatic hypocalcemia.

OBJECTIVES: To identify any risk factors for incidental parathyroidectomy and to define its association with symptomatic postoperative hypocalcemia. DESIGN: Retrospective study. SETTING: Tertiary referral cancer center. PATIENTS: Consecutive patients who underwent thyroid surgery between 1991 and 1999. Patients who underwent procedures for locally advanced thyroid cancer requiring laryngectomy, tracheal resection, or esophagectomy were excluded. INTERVENTIONS: All pathology reports were reviewed for the presence of any parathyroid tissue in the resected specimen. Slides were reviewed, and information regarding patient demographics, diagnosis, operative details, and postoperative complications was collected. MAIN OUTCOME MEASURE: Identification of parathyroid tissue in resected specimens and postoperative symptomatic hypocalcemia. RESULTS: A total of 141 thyroid procedures were performed: 69 total thyroidectomies (49%) and 72 total thyroid lobectomies (51%). The findings were benign in 68 cases (48%) and malignant in 73 cases (52%). In the entire series, incidental parathyroidectomy was found in 21 cases (15%). Parathyroid tissue was found in intrathyroidal (50%), extracapsular (31%), and central node compartment (19%) sites. The performance of a concomitant modified radical neck dissection was associated with an increased risk of unplanned parathyroidectomy (P =.05). There was no association of incidental parathyroidectomy with postoperative hypocalcemia (P =.99). Multivariate analysis identified total thyroidectomy as a risk factor for postoperative hypocalcemia (P =.008). In the entire study group, transient symptomatic hypocalcemia occurred in 9 patients (6%), and permanent hypocalcemia occurred in 1 patient who underwent a total thyroidectomy and concomitant neck dissection. CONCLUSIONS: Unintended parathyroidectomy, although not uncommon, is not associated with symptomatic postoperative hypocalcemia. Modified radical neck dissection may increase the risk of incidental parathyroidectomy. Most of the glands removed were intrathyroidal, so changes in surgical technique are unlikely to markedly reduce this risk.

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.

PURPOSE: The optimal fractionation schedule for radiotherapy of head and neck cancer has been controversial. The objective of this randomized trial was to test the efficacy of hyperfractionation and two types of accelerated fractionation individually against standard fractionation. METHODS AND MATERIALS: Patients with locally advanced head and neck cancer were randomly assigned to receive radiotherapy delivered with: 1) standard fractionation at 2 Gy/fraction/day, 5 days/week, to 70 Gy/35 fractions/7 weeks; 2) hyperfractionation at 1. 2 Gy/fraction, twice daily, 5 days/week to 81.6 Gy/68 fractions/7 weeks; 3) accelerated fractionation with split at 1.6 Gy/fraction, twice daily, 5 days/week, to 67.2 Gy/42 fractions/6 weeks including a 2-week rest after 38.4 Gy; or 4) accelerated fractionation with concomitant boost at 1.8 Gy/fraction/day, 5 days/week and 1.5 Gy/fraction/day to a boost field as a second daily treatment for the last 12 treatment days to 72 Gy/42 fractions/6 weeks. Of the 1113 patients entered, 1073 patients were analyzable for outcome. The median follow-up was 23 months for all analyzable patients and 41.2 months for patients alive. RESULTS: Patients treated with hyperfractionation and accelerated fractionation with concomitant boost had significantly better local-regional control (p = 0.045 and p = 0.050 respectively) than those treated with standard fractionation. There was also a trend toward improved disease-free survival (p = 0.067 and p = 0.054 respectively) although the difference in overall survival was not significant. Patients treated with accelerated fractionation with split had similar outcome to those treated with standard fractionation. All three altered fractionation groups had significantly greater acute side effects compared to standard fractionation. However, there was no significant increase of late effects. CONCLUSIONS: Hyperfractionation and accelerated fractionation with concomitant boost are more efficacious than standard fractionation for locally advanced head and neck cancer. Acute but not late effects are also increased.

Prolonged response to antisense cyclin D1 in a human squamous cancer xenograft model.

Local recurrence of squamous cell cancer (SCC) causes high morbidity and is often readily accessible, making such patients potential candidates for gene therapy. Cyclin D1 (CD1), critical in the G1-S transition in the cell cycle, is amplified in 20-50% and overexpressed in up to 80% of head and neck SCC. Our earlier studies indicated that CD1 expression increased with progression from low grade to high grade dysplasia, and that treatment of established tumors with antisense cyclin D1 (AS-cyclin D1) led to tumor regression during a one week evaluation period. We hypothesized that: 1) CD1 expression increases with disease progression to advanced SCC, and 2) AS-cyclin D1 therapy would lead to prolonged tumor regression in a xenograft model of human SCC. CD1 expression, evaluated by immunostain in 30 stage III/IV head and neck SCC, increased in the basal layer from normal-dysplasia (P = 0.06) and from dysplasia-carcinoma (P = 0.004). In the germinative layer CD1 expression increased from dysplasia-carcinoma (P = 0.002) but not from normal-dysplasia. Western blotting of eight SCC and two transformed keratinocyte cell lines demonstrated CD1 overexpression in 8/10 (80%) lines. An 11th cell line (A431) had previously been shown to overexpress cyclin D1. 8/9 (89%) cell lines overexpressing CD1 formed tumors in immunodeficient mice, whereas 0/2 cell lines without CD1 overexpression formed a tumor. Three established SCCs, one fast growing, one with moderate growth rate (with CD1 overexpression) and one slow growing (without increased CD1), shrank significantly for 2-4 weeks after AS-cyclin D1 treatment, while tumors transduced with control vector grew. Cyclin D1 expression increases in frequency with disease progression, and antisense cyclin D1 was effective in a xenograft model of human cancer, independent of tumor growth rate.

Primary extraosseous cemento-ossifying fibroma of the auricle.

BACKGROUND: A mass of the auricle is uncommon. An enlarging lesion may be the result of a reactive process, or a benign or malignant neoplasm. The literature is reviewed, and a case of extraosseous cemento-ossifying fibroma of the auricle is presented. METHODS: A 22-year-old white man presented with a 3-month history of an enlarging 2 cm mass in the right concha cavum. An incisional biopsy demonstrated cemento-ossifying fibroma. The lesion was resected en bloc, and the patient did well. There is no evidence of recurrence. RESULTS: Pathological examination of the excised mass revealed a well-circumscribed but unencapsulated spindle cell lesion with foci of osteoid and cementum deposition. It did not involve the auricular cartilage, and there was no connection with the overlying epidermis. CONCLUSIONS: This is a case report of an extraosseous cemento-ossifying fibroma of the auricle. This benign tumor should be completely excised because local recurrence may otherwise result.

Biliary CA 19-9 values correlate with the risk of hepatic metastases in patients with adenocarcinoma of the pancreas.

Serum values of the tumor-associated antigen CA 19-9 are useful as an independent predictor of survival in patients with adenocarcinoma of the pancreas. However, the utility of biliary CA 19-9 values is unknown. This study was undertaken to determine whether biliary CA 19-9 levels are predictive of hepatic metastases. Between 1991 and 1996, thirty-eight patients treated for adenocarcinoma of the pancreas were evaluated using a biliary CA 19-9 assay. Bile was obtained from percutaneous stents placed during the perioperative period. Five of the 38 patients had low serum levels of CA 19-9 (<2 U/ml) and were excluded from the study. Twenty-seven (80%) of the 33 patients developed distant metastases: five pulmonary, five peritoneal, and 17 hepatic. Liver metastases were discovered initially in 10 and after resection of the primary tumor in seven (median interval 10 months). Biliary CA 19-9 values were significantly higher in patients with hepatic metastases (median 267, 400 U/ml; range 34,379 to 5,000,000 U/ml) compared to patients without metastatic disease (median 34,103 U/ml; range 6,620 to 239, 880 U/ml; P <0.006). Patients with hepatic, peritoneal, and pulmonary metastases had median survivals of 8,14, and 35 months, respectively (P <0.0041). All patients without metastatic disease are alive (median follow-up 13 months). Biliary CA 19-9 values are associated with a stepwise increase in the risk of developing metastatic disease. Patients with biliary CA 19-9 levels greater than 149,490 U/ml have an increased risk of developing recurrent disease in the liver and may warrant further hepatic evaluation or therapy.

The use of processed allograft dermal matrix for intraoral resurfacing: an alternative to split-thickness skin grafts.

BACKGROUND: The standard reconstruction of significant mucosal defects in head and neck surgery has been split-thickness skin grafting (STSG). OBJECTIVE: To examine the use of a commercially available acellular dermal matrix as an alternative to STSG to reduce the scarring and contracture inherent to meshed split-thickness autografting and avoid the additional donor site morbidity. PATIENTS AND METHODS: Twenty-nine patients with full-thickness defects of the oral cavity were included in this retrospective chart review. Candidate patients had their operative procedure performed at a tertiary care center during a 24-month period. Allograft dermal matrix, an acellular tissue-processed biomaterial, was applied to these intraoral defects. The defects were reconstructed with an acellular dermal graft matrix in the same technical fashion as with an autologous skin graft. Patients were evaluated for rate of "take," functional return time to reepithelialization, average surface area of graft, associated pain and discomfort, evidence of restrictive graft contracture, patient diagnosis, and graft location within the oral cavity. Any evidence of incomplete graft reepithelialization was considered grounds for graft failure, either complete or incomplete. Epithelialization and contracture were assessed during outpatient clinical examinations. Patient complaints with regard to discomfort at the graft bed were considered evidence of pain. RESULTS: Graft locations included 9 in the tongue (32%), 5 in the maxillary oral vestibule (17%), 4 in the mandible (14%), 4 in the floor of mouth (14%), 3 in the hard and/or soft palate (10%), 3 in the tonsil (10%), and 1 in the lip (3%). The overall rate of take was 90% with complete epithelialization noted on clinical evaluation within 4 weeks. Patients were followed up for an average of 8.6 months. The average grafted surface area was 25 cm2. Pain or discomfort was noted in 3 patients (12%). One patient (4%) was noted to have clinical evidence of graft contracture. CONCLUSIONS: Allograft dermal matrix was successful as a substitute to autologous STSG for resurfacing of intraoral defects. Allograft dermal matrix may be considered a useful reconstructive option for patients with oral mucosal defects.

Radiologic staging of gastrointestinal cancer.

Pre-operative staging should define the probable course of a patient's disease, separate the resectable from the unresectable patients, and identify the patients who are candidates for induction therapy. Pre-operative staging must be well tolerated and should provide new or important information that will affect the proposed treatment plan. For some diseases such as colon cancer, pre-operative staging is largely unnecessary, but it can be of great value for other tumors such as pancreatic cancer. Currently, many imaging techniques are available to evaluate gastrointestinal cancers, and each provides information necessary for directing treatment. Although no individual technique can stage patients with complete accuracy, combinations of the various imaging techniques can be used to increase accuracy and promote appropriate decisions about an individual's treatment options. The use of current imaging techniques for staging primary lesions, regional spread, and the intra-abdominal metastatic spread of the most common gastrointestinal malignancies are reviewed.

Phase II study of N-phosphonacetyl-L-aspartate, recombinant interferon-alpha, and fluorouracil infusion in advanced squamous cell carcinoma of the head and neck.

BACKGROUND: 5-Fluorouracil (5-FU), as a single agent, produces a 15% response rate in advanced squamous cell carcinoma of the head and neck (SCCHN). N-phosphonacetyl-L-aspartate (PALA) inhibits pyrimidine biosynthesis and increases incorporation of 5-FU metabolites into ribonucleic acid (RNA). Recombinant alpha interferon-2b (rIFN-alpha-2b) may inhibit 5-FU clearance and blunt reflex rise in thymidylate synthetase, therefore enhancing inhibition of the target enzyme of 5-FU. METHODS: In an attempt to exploit their potential therapeutic synergy, we initiated a phase II trial combining PALA 250 mg/m2 by intravenous (IV) bolus day 1 with 5-FU 2600 mg/m2 24-hour IV infusion initiated 24 hours after PALA, followed by rIFNalpha-2b 10 million units (MU) by subcutaneous injection days 2, 3, and 4 in patients with advanced, measurable SCCHN incurable with surgery or radiotherapy. Treatment was repeated weekly; patients were assessed every 4-6 weeks. Pretreatment tumor specimens were analyzed for p53 mutations in exons 5-8 and for protein expression using the p53 polyclonal antibody CM-1. RESULTS: Nineteen patients were enrolled from November 1991 through February 1994. Median age was 59 years (range, 31-72 years). All had previously received definitive radiotherapy, and all but two had undergone surgical resection. Seven patients (37%) had received prior adjuvant chemotherapy. Median time from initial diagnosis to protocol enrollment was 17 months (range, 5 months to 10 years). Median performance status (PS) was 1. Primary tumor sites included oral cavity (8 patients), larynx (7 patients), oropharynx (3 patients), and hypopharynx (1 patient). The median serum transferrin was 241 (range, 141-333). Sixteen patients (84%) had sufficient pretreatment biopsy material for p53 analysis. Patients received a median of 6 weeks of treatment (range, 2-30 weeks). Six patients (32%) in the absence of disease progression failed to finish the first 6 weeks of treatment: 3 died of pulmonary insufficiency or pneumonia and 3 were removed from study during the first 6 weeks due to toxicity. Grade 2-3 flulike symptoms occurred in 17 patients (89%); grade > or = 3 fatigue occurred in 12 patients (63%), and grade > or = 2 stomatitis occurred in 5 (26%). Gastrointestional toxicity was minimal and myelosuppression mild. Of 13 evaluable patients, there were 2 partial responses (15%) lasting 3 months and 20 months; 5 patients with stable disease lasting 2, 2, 2.5, 3, and 4.5 months; and 6 with disease progression. For all 19 patients, the overall response rate was 11%, the median survival was 6 months and 1-year survival rate 26%. Lower transferrin values (< or =241) were associated with shortened median survival 2.5 vs 11 months). Increased p53 protein expression but not p53 mutations in pretreatment specimens also predicted inferior survival (median, 6 vs 11 months) after enrollment in study (p = .0124). CONCLUSIONS: Biochemical modulation of 5-FU by rIFNalpha-2b and PALA does not enhance its efficacy in patients with advanced SCCHN whose disease has progressed after prior radiotherapy. Serum transferrin and p53 protein expression segregate outcome in this group of uniformly treated patients.

Surgical management of local and regional recurrent head and neck squamous cell carcinoma.

During 1997 more than 40,000 Americans developed a squamous cancer of the upper aerodigestive tract. Surgery and radiation therapy may have been used alone or together, with reasonable prospects for curing them of disease. The majority of patients whose cancer cannot be controlled are confronted with local or regional recurrence. Such recurrences often occur in sites of the head and neck that are suited to early detection during an office examination. Hence, many are treatable with curative intent. This review addresses various surgical approaches to these difficult management problems.