The National Cancer Data Base Report on Cancer of the Head and Neck

ORIGINAL ARTICLE The National Cancer Data Base Report on Cancer of the Head and Neck

Henry T. Hoffman, MD; Lucy Hynds Karnell, PhD; Gerry F. Funk, MD; Robert A. Robinson, MD; Herman R. Menck, MBA

Background: The National Cancer Data Base (NCDB), Results: The largest proportion of cases arose in the lar- a large sample of cancer cases accrued from hospital- ynx (20.9%) and oral cavity, including lip (17.6%) and based cancer registries, is sponsored by the Commis- thyroid gland (15.8%). Squamous cell carcinoma (55.8%) sion on Cancer of the American College of Surgeons and was the most common histological finding, followed by the American Cancer Society. The NCDB permits a de- adenocarcinoma (19.4%) and lymphoma (15.1%). In- tailed analysis of case-mix, treatment, and outcome vari- come level (low), race (African American), and tumor ables. grade (poorly differentiated) were most notably associated with advanced stage. Treatment was most com- Objective: To provide an overview of the contempo- monly surgery alone (32.4%), combined surgery with ir- rary status of the subset of patients with head and neck radiation (25.0%), and irradiation alone (18.9%). Overall cancer in the United States. 5-year, disease-specific survival was 64.0%. Cancer of the lip demonstrated the best survival (91.1%) and cancer Methods: The NCDB, which obtains data from US as of the hypopharynx the worst survival (31.4%). well as Canadian and Puerto Rican hospitals, accrued 4 583 455 cases of cancer between 1985 and 1994. Of these Conclusions: This NCDB analysis of cancer of the head cases, 301 350 (6.6%) originated in the head and neck. and neck provides a contemporary overview of head and We address 295 022 cases of head and neck cancer lim- neck cancer in the United States. It also serves to intro- ited to the 50 United States and District of Columbia. Cases duce a series of NCDB articles that address specific ana- were segregated into an earlier group (1985-1989) to per- tomical sites and histological types through separate, de- mit 5-year follow-up and into a later group (1990- tailed analysis. 1994) to analyze a more contemporary group. Compari- son between both periods permits identification of trends. Arch Otolaryngol Head Neck Surg. 1998;124:951-962

HE NATIONAL Cancer Data Although there is no current system Base (NCDB) is a large for gathering incidence data for the en- sample of cancer cases ac- tire United States, a population-based reg- crued from hospital-based istry termed the Surveillance, Epidemiol- cancer registries in the ogy, and End Results program9 exists to TUnited States. This database is jointly spon- provide estimates of cancer-related inci- sored by the American College of Sur- dence and mortality. This program, which geons’ Commission on Cancer (COC) and was mandated by the National Cancer Act the American Cancer Society. It is de- of 1971, currently surveys 14 distinct signed to provide descriptive information population groups representing approxi- about the demographic, management, and mately 14% of the population.10 outcome variables characterizing cancers The Surveillance, Epidemiology, and From the Departments of involving all ethnic groups in all 50 states. End Results and the NCDB programs are Otolaryngology–Head and National cancer registries have been func- separate cancer data systems that are de- Neck Surgery (Drs Hoffman, tioning for many years in other countries. signed for different purposes and rely on Karnell, and Funk) and The most highly developed registries cur- different methodologies.11 The Surveil- Pathology (Dr Robinson), rently exist in European countries with lance, Epidemiology, and End Results pro- University of Iowa Hospitals small populations that include Sweden, gram is a population-based registry that is and Clinics, Iowa City; and 1-6 National Cancer Data Base, Norway, and Denmark. In 1988 the intended to accurately sample a measur- Commission on Cancer of the United States established its national clini- able segment of the US population. The American College of Surgeons, cal cancer registry with the creation of the NCDB is a hospital-based registry that Chicago, Ill (Mr Menck). NCDB.7,8 monitors patterns from a much larger pa-

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 MATERIALS AND METHODS cancer. Although patients are followed up longitudinally and recurrent disease is added to their record if identified, the The NCDB data are collected yearly on a voluntary basis NCDB does not collect records of patients who were iden- through a computerized format from hospital-based can- tified at the reporting hospital with recurrent disease. To en- cer registries.7 The NCDB cancer registry data are coded sure that the database does not include more than 1 record according to schemata published in the Data Acquisition for each patient (eg, a patient having received primary treat- Manual,14,15 the first through the fourth editions of the Ameri- ment at 2 different reporting hospitals), an algorithm based can Joint Committee on Cancer (AJCC) Manual for Stag- on patient and disease characteristics was used to identify ing of Cancer,16-19 and the second edition of the Interna- and remove these duplicate records. tional Classification of Disease for Oncology (ICD-O 2).20 Patterns of presentation and treatment across time are The head and neck cancer data set was defined by the investigated by dividing the years of diagnosis into an ear- ICD-O 2 topography codes and included the lip, oral cavity, lier period (1985-1989) and a later period (1990-1994). oropharynx, nasopharynx, hypopharynx, and major sali- Case-mix characteristics and treatment are stratified by ana- vary glands (C00.0-14.8), sinonasal tract (C30.0, 31.0- tomical site and extent of disease, when appropriate, to pro- 31.9), and larynx (C32.0-32.9). Although the lip is included vide a more detailed analysis. with other subsites in the oral cavity according to AJCC stag- Patients were classified by geographic regions that were ing, its behavior is sufficiently different from the remainder organized by grouping individual states into 6 regions as of the oral cavity that it was considered separately in this ar- previously reported.7 Income was inferred for each pa- ticle. Other head and neck sites included in the head and neck tient based on the average family income of the ZIP code data set were the middle ear (C30.1), trachea (C33.9), eye of residence. To compare the level of income of patients and ocular adnexa (C69.0-69.9), olfactory nerve (C72.2), thy- with head and neck cancer with the income of all patients roid gland (C73.9), parathyroid glands (C75.0), and other with cancer within the NCDB, 3 income groups were cre- endocrine gland–related structures (C75.2, C75.4-75.9), ex- ated. These income groups were chosen to approximate the cluding the pineal and pituitary glands. Additional sites iso- lowest 10%, the highest 10%, and intermediate incomes for lated to the head and neck included bones, joints, and ar- all NCDB cases.21 The low-income group included pa- ticular cartilages (C41.0-41.9), peripheral nerves and tients with annual incomes of less than $20 000 that rep- autonomic nervous system (C47.0), connective, subcutane- resented 11.2% of the NCDB data set. The high-income ous, and other soft tissues (C49.0), and lymph nodes (C77.0). group included patients with annual incomes of $47 000 The nonspecific sites within the head and neck classified as or more, which represented 10.3% of the NCDB data set. “other” and “ill-defined” (C76.0) were also included. Extent of disease was represented by “combined stage” The reporting hospitals provide only those cases that that reflects pathologic staging (pAJCC stage group) when were diagnosed and/or treated at their institute as a primary it was available through the reporting cancer registrar’s

tient base derived from community hospitals, teaching the potential to be affected by a selection bias that could hospitals, and cancer centers.8 skew the sampling of cases. Despite these potential limi- The goal of the NCDB is to improve cancer man- tations in data collection, the large numbers of cases ac- agement through analysis of data characterizing a large crued offer demographic, management, and outcome in- proportion of all cases of cancer in the United States. To formation from a broad spectrum of treating facilities in help achieve this goal, the NCDB has established the ob- the United States. A recent comparison between NCDB and jective to collect 80% of all US incident cancers by the Surveillance, Epidemiology, and End Results data identi- year 2000. The first call for data by the NCDB yielded fied patterns that differed only marginally in the analysis an estimated 24% of all cancer cases diagnosed in 1985. of breast, colorectal, lung, and prostate cancers evaluated This sample represented 232 577 cases reported from 501 for the diagnostic year 1992.11 hospitals. The number of participating NCDB hospitals We address the subset of the NCDB cancer cases lim- and cases accrued for the year 1994 increased to 1227 ited to the head and neck. Most cancers commonly hospitals reporting 689 714 cases, reflecting an esti- grouped as head and neck malignancies arise from the mated 57% of all cancer cases. This increase in report- mucosal lining of the upper aerodigestive tract and the ing over the past 9 years has paralleled an increase in the adjacent salivary glands. Thyroid, parathyroid, sinona- number of hospital cancer registries that have become sal, and ocular cancers are also considered cancers of the computerized. head and neck. In addition to cancers arising in these sites, An additional impetus to increased reporting of cases lymphomas and other less common tumors that arise from is a mandate established by the COC. Since 1997, all hos- the adjacent soft tissue, bone, and cartilaginous struc- pitals participating in the COC’s approvals program are tures in the head and neck region are considered in this required to submit data to the NCDB. Continued expan- article. Skin cancers that occur in the head and neck re- sion in the accrual of cases is anticipated as more hos- gion are not included in this review. Brain malignancies pitals fulfill these requirements. are not generally classified as cancers of the head and neck Before 1997 the COC did not require reporting of data and are also not considered herein. to the NCDB. The NCDB obtained reports on a voluntary To date, reports from the NCDB of cancers of the basis from those institutions that elected to contribute data head and neck have been limited to the larynx12 and thy- from their cancer registries. As a result, the database prior roid gland.13 We present the first analysis of the NCDB to 1997 must be considered a convenience sample with providing a broad review of cancer of the head and neck.

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 review of the chart, and clinical stage (cAJCC stage group) is used. As a result, a neoplasm considered poorly differ- when pathologic stage was not recorded or not appropri- entiated with areas that are undifferentiated would be con- ate. Cases were broadly grouped into general histological sidered grade 4 (undifferentiated or anaplastic). Cases with- categories according to the ICD-O 2 morphologic codes. out numeric grading but described as low grade or partially These groups were carcinoma not otherwise specified (NOS) well differentiated are considered grades 1 to 2, and there- (M8010, M8012-8022), squamous cell carcinoma (M8052- fore are recorded as grade 2. Cases described as medium 8082), verrucous carcinoma (M8051), adenocarcinoma grade are considered to be grades 2 to 3, and therefore are (M8140-8580), and lymphoma (M9590-9723). All other coded as grade 3. Moderately differentiated or relatively un- histological codes for these head and neck sites were com- differentiated cancers are considered grade 3 and coded as bined into a category labeled other. such. Cases listed as high grade are considered grades 3 to A substantial proportion of thyroid cancers were cat- 4, and therefore are recorded as grade 4.15,22 egorized as “papillary carcinoma, NOS” (M8050), which Treatment presented in this report is limited to the first is a subset of squamous cell carcinomas. Analysis of the da- course of cancer-directed therapy used to manage the pri- tabase indicated that 99.6% of the papillary carcinoma, NOS mary tumor. This initial cancer-directed therapy may in- cases were thyroid in origin. This classification of thyroid clude a combination of modalities and may span many weeks papillary carcinoma as a subset of squamous cell carci- or several months if irradiation or multiple cycles of che- noma was interpreted as a coding error. As a result, thy- motherapy are included in the original treatment plan. Sub- roid cancers coded as papillary carcinoma, NOS (M8050) sequent therapy to address recurrences is not included herein. were recoded as papillary adenocarcinoma, NOS (M8260). All analyses were performed using SPSS statistical soft- Although distinct grading schemes are used for can- ware.23 Survival analyses represent annual disease- cers that differ by specific morphologic and anatomical site specific rates with the date of diagnosis as the starting point grouping, the NCDB uses the World Health Organiza- and the date of death with cancer as the end point. For the tion’s20 standard grading system. This system provides 4 purposes of this survival analysis, it was assumed that the separate grades (and the additional category “unknown”) cause of death was cancer for those patients whose status for all cancers except lymphomas and leukemias. Through at last follow-up was recorded as dead with cancer. ␹2 Sta- review of pathology reports, hospital-based cancer regis- tistics were performed on selected contingency tables and trars assign grade 1 (well differentiated), grade 2 (moder- pairwise comparisons were performed on selected sur- ately differentiated, moderately well differentiated, or in- vival rates. Because of the large number of patients within termediate differentiation), grade 3 (poorly differentiated), this sample, all resultant PϽ.0001. Therefore, no inferen- grade 4 (undifferentiated or anaplastic), or grade “un- tial statistics were reported. Instead, most data were pre- known” to all cases. According to this scheme, when chart sented in stratified form (eg, cross-tabulations) so that clini- review reveals 2 different degrees of grading, the higher code cally relevant associations could be directly assessed.

RESULTS 1985 232 577 All Cases 15 873 Cases of Head 238 157 1986 and Neck Cancer 16 936 Cancers of the head and neck represented 6.6% of all 1987 322 117 24 351 NCDB cases between 1985 and 1995 (range, 6.1%-7.6% 1988 461 544 per year) (Figure 1). From these overall counts, cases 32 053 1989 468 805 from reporting hospitals outside the United States (ie, 31 907 Year 1990 408 372 Canada and Puerto Rico) were excluded from analysis, 28 054 dropping the total number to 295 022. Approximately 25% 1991 509 958 of the patients with cancer of the head and neck were 31 993 1992 634 669 accrued from smaller community hospitals, 33% from 38 678 1993 617 542 larger community hospitals, 33% from teaching and Na- 38 633 tional Cancer Institute–designated institutes, and the re- 1994 689 714 maining 9% from other types of hospitals (eg, free- 42 872 standing cancer programs). Figure 1. Reported cancers by diagnosis year.

PATIENT CHARACTERISTICS was a concurrent decrease from 4.4% to 4.0% in patients labeled “other/unknown.” Reporting from the 6 re- Demographic data were segregated into 118 292 cases gions of the United States was lowest from the Moun- from the earlier period (1985-1989) and 176 730 cases tain region (16 692 cases) and highest from the Midwest from the more current period (1990-1994). Age distri- (71 377 cases). bution remained stable across the years, with the 60- to Income groupings were designed to broadly clas- 69-year-old cohort representing the largest percentage sify patients according to an approximation of the low- of cases (27.0%) (Table 1). Males outnumbered fe- est and highest 10% of annual family incomes in the males at a ratio of approximately 1.5:1 that remained stable United States. Patients with cancer of the head and neck across the periods studied. The proportion of patients con- were disproportionately overrepresented in the lower- sidered non-Hispanic African American increased from income group (13.8%) and underrepresented in the 8.0% to 8.8% from the earlier to the later period. There higher-income group (9.6%). The income grouping of

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Characteristic 1985-1989 1990-1994 Total Age, y Ͻ30 8004 (6.8) 11 298 (6.4) 19 302 (6.5) 30-39 8129 (6.9) 13 660 (7.7) 21 789 (7.4) 40-49 12 449 (10.5) 20 724 (11.7) 33 173 (11.2) 50-59 22 834 (19.3) 31 981 (18.1) 54 815 (18.6) 60-69 33 397 (28.2) 46 140 (26.2) 79 537 (27.0) 70-79 23 878 (20.2) 36 835 (20.8) 60 713 (20.6) Ն80 9308 (7.9) 15 666 (8.9) 24 974 (8.5) Unknown 293 (0.2) 426 (0.2) 719 (0.2) Total 118 292 (100) 176 730 (100) 295 022 (100) Sex Male 71 561 (60.5) 105 334 (59.6) 176 895 (60.0) Female 46 495 (39.3) 71 145 (40.3) 117 640 (39.8) Unknown 236 (0.2) 251 (0.1) 487 (0.2) Total 118 292 (100) 176 730 (100) 295 022 (100) Race/ethnicity White non-Hispanic 100 393 (84.8) 148 134 (83.8) 248 527 (84.3) African American, non-Hispanic 9426 (8.0) 15 541 (8.8) 24 967 (8.5) Hispanic (any race) 3314 (2.8) 5975 (3.4) 9289 (3.1) Other/unknown 5159 (4.4) 7080 (4.0) 12 239 (4.1) Total 118 292 (100) 176 730 (100) 295 022 (100) Income† Low, Ͻ$20 000 15 513 (13.8) 23 305 (13.9) 38 818 (13.8) Middle, $20 000-46 999 86 921 (77.0) 127 886 (76.3) 214 807 (76.6) High, Ն$47 000 10 375 (9.2) 16 277 (9.8) 26 652 (9.6) Subtotal Known Income 112 809 (100) 167 468 (100) 280 277 (100) Other/unknown 5483 (4.6)† 9262 (5.2)† 14 745 (5.0)‡ Total 118 292 176 730 295 022 Geographic region Northeast 20 998 (17.8) 34 435 (19.5) 55 433 (18.8) Southeast 20 385 (17.2) 34 515 (19.5) 54 900 (18.6) Midwest 29 690 (25.1) 41 687 (23.5) 71 377 (24.1) South 16 440 (13.9) 30 327 (17.2) 46 767 (15.9) Mountain 7919 (6.7) 8773 (5.0) 16 692 (5.7) Pacific 22 860 (19.3) 26 993 (15.3) 49 853 (16.9) Total 118 292 (100) 176 730 (100) 295 022 (100)

*All values are presented as number (percentage). †Income grouping based on the lowest (Ͻ$20 000) and highest (Ն$47 000) 10% of all patients with cancer from the National Cancer Data Base data set. ‡Percentages based on total cases.

patients varied substantially according to the anatomi- Table 2. Anatomical Site by Income for Patients cal site of the cancer (Table 2). Except for those pa- With Cancer of the Head and Neck (All Years)* tients with nasopharyngeal cancer, more than 15% of all patients with pharyngeal cancer were considered low in- Income Level come. The sites with the greatest proportion of patients Site Cases Low Middle High Unknown in the high-income category were the thyroid gland Lip 10 274 15.1 74.8 5.1 5.0 (12.8%), other (10.6%), and major salivary glands (9.8%). Oral cavity 41 490 13.7 73.2 8.2 4.9 Oropharynx 36 271 15.3 71.5 8.2 5.0 DISEASE CHARACTERISTICS Nasopharynx 7557 13.2 71.4 9.7 5.7 Hypopharynx 12 581 15.6 71.6 7.6 5.2 The largest number of tumors arose in the larynx (20.8%) Pharynx, NOS† 4393 15.4 72.0 7.4 5.2 and was followed in decreasing order by the oral cavity, Larynx 61 778 15.4 72.8 7.1 4.7 Major salivary gland 13 185 11.7 73.8 9.8 4.7 including lip (17.6%), thyroid gland (15.8%), and the oro- Thyroid gland 46 648 9.3 72.8 12.8 5.1 pharynx (12.3%) (Table 3). The major salivary glands, Sinonasal 8932 13.4 72.1 8.7 5.8 which include the submandibular, sublingual, and pa- Eye and adnexa 9360 12.3 72.9 8.6 6.2 rotid glands, were the site of origin in 4.5% of cases. The Other 42 553 11.0 73.5 10.6 4.9 predominant histological type was squamous cell carcinoma, which represented 55.8% of all cases. Adenocar- *Income grouping based on the lowest (Ͻ$20 000) and highest cinomas demonstrated the largest proportional change (Ն$47 000) 10% of all patients with cancer on the National Cancer Data Base data set. All data are presented as percentages. in histological types across the 2 periods; the increase from †NOS indicates not otherwise specified. 18.2% to 20.3% represented an 11.5% proportional change

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Characteristic 1985-1989 1990-1994 Total Site Lip 4375 (3.7) 5899 (3.3) 10 274 (3.5) Oral cavity 17 341 (14.7) 24 149 (13.7) 41 490 (14.1) Oropharynx 14 443 (12.2) 21 828 (12.4) 36 271 (12.3) Nasopharynx 3069 (2.6) 4488 (2.5) 7557 (2.6) Hypopharynx 5225 (4.4) 7356 (4.2) 12 581 (4.3) Pharynx, NOS 1918 (1.6) 2475 (1.4) 4393 (1.5) Larynx 25 577 (21.5) 36 201 (20.5) 61 778 (20.8) Major salivary glands 5160 (4.4) 8025 (4.5) 13 185 (4.5) Thyroid gland 17 157 (14.5) 29 491 (16.7) 46 648 (15.8) Sinonasal 3611 (3.1) 5321 (3.0) 8932 (3.0) Eye and adnexa 3383 (2.9) 5977 (3.4) 9360 (3.2) Other 17 033 (14.4) 25 520 (14.4) 42 553 (14.4) Total 118 292 (100) 176 730 (100) 295 022 (100) Histological findings Squamous cell carcinoma 68 114 (57.6) 96 360 (54.5) 164 474 (55.8) Adenocarcinoma 21 480 (18.2) 35 799 (20.3) 57 279 (19.4) Verrucous cancer 739 (0.6) 971 (0.5) 1710 (0.6) Carcinoma, NOS 3104 (2.6) 4687 (2.7) 7791 (2.6) Lymphoma 17 420 (14.7) 27 165 (15.4) 44 585 (15.1) Other 7435 (6.3) 11 748 (6.6) 19 183 (6.5) Total 118 292 (100) 176 730 (100) 295 022 (100) “Combined” stage† 0 2013 (2.9) 3735 (2.6) 5748 (2.7) I 25 074 (35.8) 52 452 (36.2) 77 526 (36.1) II 13 330 (19.0) 27 963 (19.4) 41 293 (19.2) III 12 257 (17.5) 23 205 (16.1) 35 462 (16.5) IV 17 384 (24.8) 37 106 (25.7) 54 490 (25.4) Subtotal Known Stage 70 058 (100) 144 461 (100) 214 519 (100) Unknown stage 48 234 (40.8)‡ 32 269 (18.3)‡ 80 503 (27.3)‡ Total 118 292 176 730 295 022 Grade, differentiation 1, Well 17 527 (26.8) 23 923 (24.2) 41 450 (25.3) 2, Moderate 28 224 (43.1) 44 760 (45.4) 72 984 (44.5) 3, Poor 16 866 (25.8) 25 523 (25.9) 42 389 (25.8) 4, Undifferentiated 2817 (4.3) 4463 (4.5) 7280 (4.4) Subtotal Known Grade 65 434 (100) 98 669 (100) 164 103 (100) Unknown grade 52 858 (44.7)‡ 78 061 (44.2)‡ 130 919 (44.4)‡ Total 118 292 176 730 295 022 Treatment Surgery only 38 225 (32.2) 57 329 (32.4) 95 554 (32.4) RT only 23 837 (20.2) 31 860 (18.0) 55 697 (18.9) Chemotherapy only 6498 (5.5) 9558 (5.4) 16 056 (5.4) Surgery and RT 28 499 (24.1) 45 321 (25.6) 73 820 (25.0) Surgery and chemotherapy 2283 (1.9) 3990 (2.3) 6273 (2.1) RT and chemotherapy 6501 (5.5) 11 070 (6.3) 17 571 (6.0) All 3 2791 (2.4) 4587 (2.6) 7378 (2.5) No treatment 7899 (6.7) 10 340 (5.9) 18 239 (6.2) Unknown 1759 (1.5) 2675 (1.5) 4434 (1.5) Total 118 292 (100) 176 730 (100) 295 022 (100)

*NOS indicates not otherwise specified; RT, radiation therapy. All values are presented as number (percentage). †“Combined” stage represents AJCC pathologic stage, augmented by clinical stage where pathologic stage is not available. ‡Percentage based on total cases.

in these 2 percentages. This increase paralleled a similar stage I (36.2%). A marked decrease in the proportion of increase in the proportion of thyroid cancers. A smaller cases without known stage occurred between 1985- 4.8% increase in the proportion of cases that were lym- 1989 (40.8%) and 1990-1994 (18.3%). There was virtu- phoma was noted between 1985-1989 (14.7%) and 1990- ally no change across these years in the proportion of cases 1994 (15.4%). A larger proportionate increase was noted with unknown grade. Degree of differentiation was re- for cases of lymphoma arising from the mucosal lining corded as unknown in 44.7% of 1985-1989 cases and in of the upper aerodigestive tract and adjacent salivary 44.2% of 1990-1994 cases. glands (data not shown). The most common initial management strategies Among those cases that were staged, the distribu- used were surgery alone (32.4%), surgery combined with tion remained stable across the 2 periods. Most cases were irradiation (25.0%), and irradiation alone (18.9%). In gen-

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 Table 4. Anatomical Site by Histological Features for Cancers of the Head and Neck (All Years)*

Site No. of Cases SCC Adenocarcinoma Verrucous Carcinoma, NOS Lymphoma Other Lip 10 274 87.4 2.6 0.7 1.1 0.3 7.9 Oral cavity 41 490 86.3 5.9 2.0 1.5 1.4 2.9 Oropharynx 36 271 86.7 2.6 0.2 1.9 6.8 1.8 Nasopharynx 7557 64.2 4.0 0.1 15.1 10.2 6.4 Hypopharynx 12 581 94.9 1.1 0.1 1.7 0.8 1.4 Pharynx, NOS 4393 86.0 1.8 0.3 2.3 6.3 3.3 Larynx 61 778 93.9 1.4 1.0 2.4 0.2 1.1 Major salivary gland 13 185 16.3 55.4 Ͻ0.1 6.2 13.9 8.2 Thyroid gland 46 648 0.4 92.0 Ͻ0.1 3.0 3.5 1.1 Sinonasal 8932 47.4 13.2 0.6 5.9 12.0 20.9 Eye and adnexa 9360 10.9 2.1 Ͻ0.1 2.1 18.0 66.9 Other 42 553 5.1 1.4 0.1 1.2 79.8 12.4

*SCC indicates squamous cell carcinoma; NOS, not otherwise specified. All values are presented as percentage.

eral, there was no substantial change between 1985- Stage I cancers were most common in the younger 1989 and 1990-1994 in type of treatment. However, a no- (Ͻ40 years) patients. Stage IV cancers were more com- table increase in combined radiotherapy and mon among the middle-age (50-69 years) group. Grade chemotherapy was identified across the 2 periods. This was closely associated with extent of disease when grouped combined modality approach accounted for 5.5% of pa- as early (stages I and II) and advanced (stages III and IV) tients treated in the earlier period and 6.3% of patients disease. The ratio of early-to-advanced stage was 2.4:1 treated in the more current period, reflecting a propor- for well-differentiated cancers and 0.5:1 for poorly dif- tionate increase of 14.5%. ferentiated cancers. Most cancers arising from mucosal surfaces of the Laryngeal, thyroid, lip, salivary gland, and eye and upper aerodigestive tract (lip, oral cavity, pharynx, and ocular adnexa cancers were predominately localized larynx) were squamous cell carcinoma (Table 4). Ad- (stages I and II), whereas cancers arising in the sinona- enocarcinoma was the most common histological type sal and pharyngeal sites were more commonly ad- among thyroid gland (92.0%) and major salivary gland vanced (stages III and IV). Cancers of the oral cavity were (55.4%) malignancies. Lymphoma comprised 79.8% of evenly divided between localized and advanced stages. the cases originating in the site termed other, which in- Squamous cell carcinoma and carcinoma, NOS were most cludes lymph nodes of the head, face, and neck. The pro- commonly stage IV. Adenocarcinoma, verrucous carci- portion of lymphoma cases arising at designated sites was noma, and lymphoma were most commonly stage I. greatest for eye and ocular adnexa (18.0%), major salivary glands (13.9%), sinonasal (12.0%), and nasophar- TREATMENT ynx (10.2%). Although lymphoma represented only 6.8% of cases in the oropharynx, this site was second only to The distribution of treatments varied by site (Table 6). other in the absolute number of lymphoma cases. Surgery was the most common treatment for cancers of the The number of cases classified as carcinoma, NOS lip (85.2%), thyroid gland (54.8%), eye and ocular ad- was greatest in the larynx and thyroid gland. Although nexa (50.6%), and oral cavity (46.2%). Irradiation was the the absolute number of these cases was smaller in the na- most common treatment for cancers of the nasopharynx sopharynx than the larynx or thyroid gland, the naso- (37.5%), larynx (33.0%), and oropharynx (27.3%). Com- pharyx had the largest proportion (15.1%) of carci- bined surgery with irradiation was the most common treat- noma, NOS cases. Verrucous carcinoma was most ment for major salivary glands (42.4%) and hypopharyn- common in the oral cavity and larynx, where it consti- geal cancer (29.9%). Combined chemotherapy and tuted 2.0% and 1.0% of cases, respectively. irradiation was used to treat 23.5% of nasopharyngeal, 13.2% of hypopharyngeal, and 11.4% of oropharyngeal cancers. PATIENT AND DISEASE CHARACTERISTICS Only 3.5% of patients with laryngeal cancers were treated with combined chemotherapy and irradiation. Cross-tabulations of patient and disease characteristics by stage (Table 5) indicated that a greater proportion of ad- OUTCOME vanced-stage cancers (stages III and IV) occurred among the lower-income group, the geographic region of the The overall median follow-up for all cases in the early Southeast, and African Americans. Sex also was associ- period (1985-1989) was 37 months compared with 10 ated with differences in stage distribution. There were more months for the later (1990-1994) period (Table 7). It advanced-stage cancers and fewer stage I cancers in the is clear that survival analysis would cover a limited fol- male group. These differences must be interpreted in the low-up for patients accrued in the 1990-1994 period. As context of other sex differences. Thyroid cancer, which is a result, survival analysis was limited to cases accrued dominated by early-stage disease, occurs in women more in the 1985-1989 period. Through analysis that ex- frequently than in men (data not shown). cludes the small number of patients with unknown sta-

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 Table 5. Patient and Disease Characteristics by “Combined” Stage for Cancers of the Head and Neck (All Years)*

Combined Stage No. of Unstaged No. of Characteristics 0 I II III IV Staged Cases Cases Total Cases Age, y Ͻ30 1.2 54.2 23.0 12.4 9.2 13 109 32.1 19 302 30-39 1.3 60.3 15.8 10.2 12.4 15 383 29.4 21 789 40-49 2.1 38.9 18.1 15.6 25.3 24 398 26.4 33 173 50-59 2.6 29.4 19.6 18.3 30.1 40 941 25.3 54 815 60-69 3.2 31.0 19.0 17.7 29.1 58 859 26.0 79 537 70-79 3.3 34.2 19.1 17.3 26.1 44 012 27.5 60 713 Ն80 2.9 35.2 21.3 16.5 24.1 17 441 30.2 24 974 Sex Male 3.1 32.9 18.0 17.2 28.8 130 052 26.5 176 895 Female 2.0 41.2 21.2 15.5 20.1 84 161 28.4 117 640 Race/ethnicity White, non-Hispanic 2.7 37.4 19.6 16.4 23.9 180 820 27.2 248 527 African American, non-Hispanic 2.2 23.6 16.6 17.7 39.9 18 838 24.5 24 967 Hispanic (any race) 2.3 35.8 18.4 17.1 26.4 6693 27.9 9289 Income† Low 2.5 30.6 18.4 17.7 30.8 28 529 26.5 38 818 Middle 2.7 36.5 19.3 16.5 25.0 155 090 27.8 214 807 High 2.8 41.6 19.9 15.4 20.3 20 204 16.7 24 267 Geographic region Northeast 2.6 34.1 19.2 17.2 26.9 43 799 21.0 55 433 Southeast 2.7 34.0 19.3 16.4 27.6 40 872 25.6 54 900 Midwest 2.5 37.9 19.1 16.6 23.9 50 351 29.4 71 377 South 2.6 36.0 19.5 16.9 25.0 35 380 24.3 46 767 Mountain 3.3 39.8 18.7 14.7 23.5 10 088 39.6 16 692 Pacific 3.1 37.6 19.4 15.8 24.1 34 029 31.7 49 853 Site Lip 4.3 77.3 11.4 3.7 3.3 7389 28.1 10 274 Oral cavity 3.2 30.5 21.6 15.4 29.3 31 363 24.4 41 490 Oropharynx 1.9 15.8 16.5 20.2 45.6 28 130 22.4 36 271 Nasopharynx 0.9 14.2 10.9 17.3 56.7 5506 27.1 7557 Hypopharynx 1.2 10.0 11.5 21.6 55.7 9944 21.0 12 581 Pharynx, NOS 2.2 13.7 14.9 22.5 46.7 2976 32.2 4393 Larynx 5.5 36.6 18.7 17.6 21.6 49 760 19.4 61 778 Major salivary gland 0.7 43.2 19.1 16.2 20.8 9399 28.7 13 185 Thyroid gland 0.5 56.1 22.5 13.8 7.1 35 176 24.6 46 648 Sinonasal 2.2 24.5 12.8 18.5 42.0 4286 52.0 8932 Eye and adnexa 6.1 39.8 23.6 21.0 9.5 4783 48.9 9360 Other 1.0 41.5 23.9 15.4 18.2 25 807 39.3 42 553 Grade, differentiation 1, Well 1.6 49.9 19.7 12.9 15.9 31 885 23.1 41 450 2, Moderate 0.8 28.2 19.8 19.4 31.8 57 786 20.8 72 984 3, Poor 0.7 17.0 14.9 21.6 45.8 32 166 24.1 42 389 4, Undifferentiated 0.7 16.1 14.0 19.4 49.8 5120 29.7 7280 Histological findings SCC 3.3 28.7 17.3 18.0 32.7 126 938 22.8 164 474 Adenocarcinoma 0.6 54.3 21.9 14.1 9.1 42 768 25.3 57 279 Verrucous 3.3 47.1 26.5 12.4 10.7 1237 27.7 1710 Carcinoma, NOS 19.4 15.0 9.4 13.9 42.3 5066 35.0 7791 Lymphoma 0.8 45.3 24.7 12.4 16.8 28 665 35.7 44 585 Other 1.1 36.3 21.3 21.5 19.8 9845 48.7 19 183

*NOS indicates not otherwise specified; SCC, squamous cell carcinoma. All values are presented as percentages unless otherwise noted. †Income groupings based on the lowest (Ͻ$20 000) and highest (Ն$47 000) 10% of all patients with cancer on the National Cancer Data Base data set.

tus, 49.8% of patients diagnosed in the earlier period were 64.0%. When analyzed by site, patients with cancer of dead at last contact (with or without known cancer). the lip demonstrated the highest survival rate (91.1%), Among the patients who were alive at last follow-up, whereas patients with cancer of the hypopharynx dem- 62.5% were without evidence of recurrent cancer. The onstrated the lowest survival rate (31.4%) (Figure 2 and median follow-up time for those who were alive at last Figure 3). When analyzed by histological findings contact with cancer was 44 months. (Figure 4), the highest 5-year survival was noted for Five-year, disease-specific survival for all cases of patients with adenocarcinoma (87.6%) and verrucous car- head and neck cancers diagnosed from 1985-1989 was cinoma (78.6%). The lowest survival rate was noted for

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Site No. of Cases Surgery Only RT Only CH Only Surgery and RT Surgery and CH RT and CH All 3 None Unknown Lip 10 274 85.2 4.5 0.1 5.8 0.2 0.1 0.1 2.8 1.2 Oral cavity 41 490 46.2 13.7 1.9 25.0 0.8 4.0 2.0 5.2 1.2 Oropharynx 36 271 17.7 27.3 4.5 25.8 1.9 11.4 3.9 5.8 1.7 Nasopharynx 7557 5.8 37.5 6.5 11.6 1.5 23.5 4.6 7.0 2.0 Hypopharynx 12 581 14.6 24.6 4.3 29.9 1.2 13.2 3.8 6.8 1.6 Pharynx, NOS† 4393 14.2 28.3 6.4 19.8 1.4 14.9 3.2 9.6 2.2 Larynx 61 778 23.5 33.0 1.1 29.2 0.6 3.5 1.5 6.0 1.6 Major salivary gland 13 185 36.4 6.7 2.2 42.4 2.8 1.8 3.1 3.7 0.9 Thyroid gland 46 648 54.8 2.7 0.5 34.6 1.0 1.0 1.5 3.1 0.8 Sinonasal 8932 26.5 16.5 4.1 28.5 2.7 9.9 5.5 5.0 1.3 Eye and adnexa 9360 50.6 22.8 1.9 11.5 2.3 2.2 1.9 5.4 1.4 Other 42 553 15.1 14.8 24.8 10.8 7.6 8.6 3.4 12.4 2.5

*RT indicates radiation therapy; CH, chemotherapy; and NOS, not otherwise specified. All values are percentages unless noted otherwise.

and outnumbers cancers of the oral cavity (including Table 7. Median Follow-up by Status at Last Contact cancers of the lip) at a ratio of 1.2:1. by Diagnostic Year for Cancers of the Head and Neck* It is reasonable to expect that the vast majority of cancer cases arising in the thyroid gland, pharynx, larynx, oral 1985-1989 1990-1994 cavity, and salivary glands are entered into a hospital- Median, Median, based cancer registry on diagnosis.27 In contrast, small can- Status Cases mo Cases mo cers of the lip may be evaluated and treated in physician Dead, no cancer 8159 33.0 3314 9.0 offices outside the hospital. If the analysis of the pathologi- Dead with cancer 29 881 14.0 19 338 6.0 cal findings from the biopsy or surgical excision of the lip Dead, cancer unknown 14 821 21.0 6094 8.0 cancer was not performed by a hospital-based pathologist, Alive, no cancer 33 067 66.0 64 131 12.0 Alive with cancer 4776 44.0 21 712 9.0 the case may not have been entered into a hospital regis- Alive, cancer unknown 15 080 63.0 26 991 9.0 try. As a result, the sampling of lip cancer data may not be Unknown 557 14.0 425 7.0 as complete as for the other sites of the head and neck. All cases 106 343 37.0 142 011 10.0 PATIENT CHARACTERISTICS *Follow-up is equivalent to the duration from date of diagnosis to date of last contact (or death, if applicable). The median follow-up for all cases, all years, is 13 months (N = 223 836). It is noteworthy that cancer of the head and neck disproportionately affects the elderly and individuals in the lower- patients with carcinoma, NOS (47.4%) and squamous cell income bracket. Males are also represented to a much greater carcinoma (56.9%). degree in the database than females. This sex disparity reflects the greater prevalence of squamous cell carcinoma COMMENT among males. Although cancers of the thyroid and salivary glands affect females most commonly, the overall domi- To our knowledge, this report of cancer of the head and nance of squamous cell carcinoma in the head and neck neck represents the largest to date. Although specific can- region is associated with a male predominance. cer management decisions cannot be made from such a Changes in demographic data across the 2 periods broad survey, our analysis provides a background for more were noted. A 10.0% proportionate increase in African specific forthcoming analyses of the NCDB data set ad- Americans (from 8.0% to 8.8%) and a 21.4% proportion- dressing individual histological types and sites. ate increase in Hispanic patients (from 2.8% to 3.4%) oc- Statistics addressing head and neck neoplasms are curred in the NCDB composition. These changes may par- often misinterpreted due to groupings of dissimilar tially reflect changes in the population of the United States cancers. For example, the oral cavity has frequently over the course of the study. It is likely that the changes been reported as the most common site for malignan- noted are partly due to a true increase in the incidence cies of the head and neck.24 An artificially high num- of cancer of the head and neck among these minority ber of cancers of the oral cavity has been reported as a groups.9 Other studies9,28-30 have noted the number of head result of grouping cancers of the salivary glands, the and neck mucosal cancers to be disproportionately greater oropharynx, and even the hypopharynx together with among African Americans than whites and to be increas- cancers of the oral cavity.25,26 The proper grouping of ing in this minority group. cases according to site as defined by the 1992 edition of the AJCC staging manual more accurately reflects a DISEASE CHARACTERISTICS lower proportion of cases arising in the oral cavity.19 Analysis of the NCDB data using this AJCC classifica- An 11.5% proportionate increase in the histological group tion identifies that laryngeal cancer is the most com- adenocarcinoma occurred between 1985-1989 (18.2%) mon head and neck malignancy in the United States and 1990-1994 (20.3%). This increase in adenocarcino-

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90 90

80 80

70 70

60 60

50 50 Alive, % Alive, % 40 40 Lip 30 Larynx 30 Thyroid Gland Oral Cavity Eye and Adnexa 20 Nasopharynx 20 Major Salivary Glands Oropharynx Other 10 Hypopharynx 10 Sinonasal

0 0 12345 12345 Year Year Site 1 2345Cases Lip 97.9 95.1 93.5 92.2 91.1 3309 Site 1 2345Cases Larynx 89.2 80.3 74.8 71.3 68.6 19 397 Thyroid Gland 93.9 92.3 91.0 90.3 89.5 13 765 Oral Cavity 81.8 68.0 61.9 58.4 55.8 12 979 Eye and Adnexa 95.1 88.8 84.2 80.2 76.1 2641 Nasopharynx 76.8 63.5 55.3 51.0 47.0 2430 Major Salivary Glands 87.3 78.4 73.2 69.6 66.9 3999 Oropharynx 76.7 61.3 53.5 49.2 46.1 10 833 Other Sites 84.1 75.3 70.0 65.8 62.2 13 527 Hypopharynx 68.8 48.1 39.5 34.3 31.4 3906 Sinonasal 79.2 65.1 58.7 54.8 52.4 2777

Figure 2. Five-year, disease-specific survival by site (mucosal surface of Figure 3. Five-year, disease-specific survival by site (other) for 1985-1989 aerodigestive tract) for 1985-1989 cases of head and neck cancers. cases of head and neck cancers.

mas paralleled a 13.2% proportionate increase in cases 100 of thyroid cancer (from 14.5% in 1985-1989 to 16.7% in 1990-1994). An increase in thyroid cancer world- 90 wide has been identified. Although the artifact of im- 80

proved record keeping has been implicated, it is likely 70 that other factors also account for this increase.31 A large number of children were subjected to therapeutic radio- 60 therapy for conditions such as acne and adenoid enlarge- 50 Alive, % ment before 1970. The aging of this population who had 40 been exposed to therapeutic irradiation in childhood has been cited as a primary cause for the increase in thyroid 30 Adenocarcinoma 32 Verrucous cancers. The development of more advanced diagnos- 20 Lymphoma tic methods has also been cited as instrumental in in- SCC 10 Carcinoma, NOS creasing the identified number of thyroid cancers.33 The 0 increased use of sophisticated radiographic imaging as 12345 well as expanded use of fine-needle aspirate biopsies may Year identify small, previously undetectable cancers. A 17.2% proportionate increase in eye and ocular Histological Features 1 2 3 4 5 Cases Adenocarcinoma 95.2 92.3 90.2 88.9 87.6 17 135 adnexal cancers occurred between 1985-1989 (2.9%) and Verrucous 90.8 85.6 82.5 79.8 78.6 555 1990-1994 (3.4%). The largest component of this change Lymphoma 85.4 77.6 72.2 68.0 64.1 13 787 Squamous Cell Carcinoma (SCC) 82.3 69.5 63.2 59.5 56.9 51 262 was an increase in ocular lymphoma (data not shown). Carcinoma, NOS 69.8 59.8 52.8 49.8 47.4 2419 The proportion of lymphoma cases within the entire head Figure 4. Five-year, disease-specific survival by histological findings for and neck database also increased, from 14.7% in 1985- 1985-1989 cases of head and neck cancers. NOS indicates not otherwise 1989 to 15.4% in 1990-1994. This increase in lym- specified. phoma may result from an increase in the number of cases occurring in patients with immunodeficiency that par- An increase was noted in the reporting of tumor stage allels an increase in the prevalence of human immuno- during the more recent (1990-1994) period. It is impor- deficiency virus infection, transplant operations, and use tant to note that assignment of stage as unknown does not of medical treatments (eg, chemotherapy) that affect the necessarily identify poor record keeping. Standardized AJCC immune system.34 Additionally, expanded use of immu- staging criteria have not yet been established for all sites nocytochemistry, developed to permit greater precision within the head and neck region. The high percentage of in identifying lymphoma cases, may correctly identify pa- unstaged sinonasal cases (52.0%) likely results from the tients who were previously assigned other diagnoses.35 lack of AJCC staging criteria for all but the maxillary si- The risk of developing lymphoma increases with age. It nus subsite within this region.19 The high proportion of un- has been proposed that some of the increase seen in the staged eye and ocular adnexa cancers (48.9%) is also likely population may be associated with an increase in the pro- related to lack of a recommended stage grouping for car- portion of the population who are elderly. cinoma of the eyelid and conjunctiva.

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 It has been reported that appropriate AJCC staging to combine clinical, epidemiological, and molecular re- is most often recorded for those cancers whose treat- search to identify both the social and biological factors ment is largely determined by stage.36 Accurate staging responsible for the racial differences seen. has become more important in the management of squa- Although a substantial proportion of the cases were mous cell carcinoma at most sites in the head and neck without known grade (44.4%), the large number of cases with the expanded application of treatment protocols in- for which grade was recorded permits evaluation of the vestigating use of chemotherapy and irradiation. These data. A clear association between advanced stage and protocols usually have stage-dependent inclusion crite- higher grade (lower degree of differentiation) is appar- ria. In contrast, management of cancers of the lip and sali- ent. This finding supports the generally accepted tenet vary gland continues to be determined primarily by clini- that, although the capacity to accurately assign progno- cal and pathologic features rather than general stage sis for individual cases based on tumor grade may be lim- groupings.37 It is therefore not surprising that, among the ited, the behavior of cancer in a large group of patients sites with established staging criteria, patients with can- can broadly be predicted by histological criteria.22 cers of the lip and salivary gland represented the largest proportion of cases with unknown stage. The smaller TREATMENT degree of improvement noted in grading cases across the periods may reflect the ambiguity that persists re- A wide spectrum of treatments was used for cancers within garding the importance of cancer grade. It is not widely individual sites (Table 6). It is apparent that manage- accepted that tumor grade impacts on management de- ment approaches are determined by factors other than cisions for most cancers of the head and neck. anatomical site. Tumor histological findings, stage, and The improvement in reporting stage from the ear- patient characteristics are additional critical determi- lier to the more current period has been supported by nants to management choices. the COC. As of 1998, it was mandated that continued Although there was little overall change in treat- hospital approval from the COC is dependent on comment patterns across time, the use of combined chemo- plete staging by the treating physicians of all cancers that therapy and radiation therapy expanded from 5.5% of have AJCC staging schema.36 The increased involve- cases in 1985-1989 to 6.3% in 1990-1994. This 14.5% ment of the hospitals across the country in central reg- proportionate increase resulted primarily from an ex- istries, cancer treatment protocols, and other programs panded application of this combination therapy in the that require or encourage AJCC staging will likely con- treatment of laryngeal and pharyngeal carcinoma (Table tribute to continued improvement in staging. 3). Protocols developed to preserve the larynx, phar- The 16.3% of cases of squamous cell carcinoma re- ynx, or tongue with chemotherapy and irradiation rather corded in the major salivary glands may represent an ar- than extirpative surgery have become increasingly popu- tificially high number. Although the NCDB designs its lar over the last decade.41-44 Whereas management of can- classification system by site of origin and not by site of cers at most sites with adjuvant chemotherapy has not metastatic disease, it is possible that a portion of the squa- improved cure rates, recent reports45-47 indicate that the mous cell carcinomas reported as salivary gland in ori- addition of adjuvant chemotherapy may offer more ef- gin actually represented metastases. It may be difficult fective treatment for nasopharyngeal carcinoma. to discriminate between metastatic disease to the parotid gland from an occult or previously treated skin can- OUTCOME cer and squamous cell carcinoma arising de novo within the parotid gland. Using rigid criteria to exclude metas- The median follow-up for patients from the 1985-1989 tases to the parotid gland, a retrospective review by period who were “alive without cancer” at last contact Gaughan et al38 identified that only 1.9% of parotid ma- was 66 months. Patients with the confirmed status of “alive lignancies were squamous cell carcinoma. Other re- with cancer” at last contact were followed up for a me- ports39 have identified squamous cell carcinoma to rep- dian of only 44 months. This substantially shorter du- resent up to 9% of parotid malignancies and between 2.1% ration of follow-up may indicate that a large proportion and 5.5% of submandibular malignancies. of patients recorded as being alive with cancer were lost to follow-up; it is reasonable to propose that some of those PATIENT AND DISEASE CHARACTERISTICS lost to follow-up died with cancer present. Had they not been lost to follow-up, they likely would have then been Advanced stage at the time of diagnosis was more com- been classified as dead, with cancer. mon among patients in the low-income group and the For patients with squamous cell carcinoma who fail African American racial category (Table 5). Other stud- treatment, recurrence is usually identified within the first ies25,28 have shown oral and pharyngeal cancers to be not 2 years following completion of initial treatment.48 In the only more prevalent but also more lethal among African absence of identified recurrence after this period, the Americans. It has been suggested that some of these ra- chance of control of the index cancer is sufficiently great cial differences are tied to economic disadvantage. The that the focus of further cancer surveillance is shifted to disproportionate cancer burden of minorities may be re- the greater risk of a second primary cancer develop- lated to limited access to resources, which, coupled with ing.49 Although recurrence data were not included in this unfavorable environmental and behavioral factors, leads report, data were presented that addressed the interval to a greater risk of developing cancer and failing its treat- from time of diagnosis to date of last contact or death ment.40 Walker et al30 have called for a conjoined effort (Figure 4). Most patients with squamous cell carcinoma

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 who died with disease within the 5-year follow-up pe- Reprints: Herman R. Menck, MBA, National Cancer riod did so within 2 years of diagnosis. The rate at which Data Base, Commission on Cancer of the American Col- patients died differed substantially by site and by histo- lege of Surgeons, 55 E Erie St, Chicago, IL 60610 (e-mail: logical findings. The proportion of patients who died [email protected]). within the first 2 years following diagnosis was greatest for squamous cell carcinoma and carcinoma, NOS. In con- REFERENCES trast, the survival rate for patients with adenocarcinoma was more constant across each of the intervals evalu- 1. Mork J, Thoresen S, Hilde F-L, Langmark F, Glattre E. Head and neck cancer in ated. 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