Sentinel lymph node biopsy for management of the N0 neck in oral cavity squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: The management of the clinically N0 (cN0) neck is controversial for early stage squamous cell carcinoma of the oral cavity (OSCC). This paper represents a single institution series analyzing the efficacy of sentinel lymph node biopsy (SNB) for early stage oral cavity cancers. METHODS: From 2005 to 2017, 108 patients with cN0 OSCC were treated with primary resection and SNB. Patients with positive biopsy results proceeded to neck dissection with or without adjuvant chemoradiotherapy. Mean follow-up for the entire cohort was 50.8 months (range: 8-147 months). Clinically, 56 patients were T1N0, 49 patients were T2N0, and three patients were T3N0 or greater. RESULTS: Disease-specific survival was 93% within the entire cohort. Sentinel lymph nodes were identified in 95.4% of patients. Twenty one patients had a positive biopsy. There were seven false-negative biopsies. The overall rate of nodal disease was 26%. Accuracy of node biopsy was 93%, with sensitivity of 75%, and negative predictive value of 91%. Recurrence rate was 19% (20/108), with an overall survival of 60% in this subgroup. CONCLUSION: SNB is a safe, effective, and well tolerated method for staging cN0 OSCC.

Interdigitating dendritic cell sarcoma.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare dendritic cell tumor with slightly more than 100 cases reported in the English literature. This report discusses a case of localized IDCS involving cervical lymph nodes and provides a literature review of clinicopathologic aspects and treatment outcomes.

Pectoralis major myocutaneous flap for reconstruction of circumferential pharyngeal defects.

BACKGROUND: A 270-degree partially tubed pectoralis major myocutaneous flap (PMMF) is an excellent option for total circumferential pharyngoesophageal defects in patients who are not candidates for more complex reconstructions. METHODS: Patients undergoing circumferential pharyngoesophageal reconstruction with partially tubed PMMF were reviewed. End points were stricture, fistula, resumption of oral intake, perioperative death, and recurrence. RESULTS: Eleven patients underwent 270-degree PMMF for reconstruction: 6 (55%) were men and 5 (45%) were women (mean, 62 years; range, 42-78 years). Three patients (27%) developed fistulas and 2 (18%) developed stenosis. Ten patients (91%) were able to resume adequate nutrition via oral intake. There were no perioperative deaths. CONCLUSIONS: Patients with severe comorbidities, metastatic disease, a lack of donor vessels, or a potentially hostile abdomen may not be ideal candidates for free tissue transfer. For these patients, partially tubed PMMF using the prevertebral fascia provides a reliable alternative for reconstruction with excellent functional results.

Evaluation of an intervention to enhance the delivery of smoking cessation services to patients with cancer.

We describe a brief staff training program to improve the delivery of tobacco cessation services to patients with head and neck cancers. This study utilized a quasi-experimental design to compare the delivery of smoking cessation components and outcomes among patients exposed to either usual care (UC) or an enhanced cessation (EC) program implemented following a 1-h staff education program. Of the 179 subjects enrolled, 112 were recontacted by phone 1 month after their clinic visit. More patients in EC compared to UC reported that they were asked about their smoking status (94.2% vs. 76.6%, p = 0.01), advised to quit (92.3% vs. 72.3%, p = 0.01), prescribed cessation medications (30.8% vs. 3.3%, p < 0.001), and received a support call (53.8% vs. 11.7%, p < 0.001) at the 1-month follow-up. Quit attempts and quit rates between groups were similar. The EC intervention improved the delivery of cessation services in a busy clinical setting, but this failed to increase cessation rates after 1 month.

Presurgical induction chemotherapy for squamous cell carcinoma of the tonsil.

OBJECTIVES/HYPOTHESIS: The indications for and efficacy of induction chemotherapy in the management of squamous cell carcinoma of the head and neck is controversial. With the advent of human papillomavirus (HPV)-related cancers, survival has improved significantly. Here we present a group of patients with tonsil cancer treated with induction chemotherapy followed by surgery. STUDY DESIGN: Retrospective cohort study. METHODS: Thirty-eight patients with tonsil cancer were treated with induction chemotherapy, consisting of cisplatin and docetaxel, followed by neck dissection and radical tonsillectomy. Twenty-six patients were HPV+, 28 were nonsmokers or long-term former smokers, and 28 were T1/T2. Fourteen patients required postoperative chemoradiotherapy (CRT). Median follow-up time was 4.1 years. RESULTS: A complete response to induction chemotherapy was achieved in 45% (17) of patients. In total, 76% (29/38) of patients were successfully treated: 53% (20/38) with chemotherapy and surgery alone, and 24% (9/38) required postoperative CRT. Almost 90% (23/26) of HPV+ and half (6/12) of HPV- patients are no evidence of disease (NED). HPV status is a significant prognostic factor (P = .02). Only 38% (5/13) of current smokers were NED compared to 96% (24/25) of nonsmokers (P = .0002). All HPV+ nonsmokers (20/20) were NED at last follow-up. CONCLUSIONS: In this study, the primary driver of prognosis was smoking status. HPV status and T stage were also important. The prognosis for HPV+ nonsmokers is extremely good; most likely regardless of treatment. Treatment failures have a poor chance of salvage, irrespective of treatment type. With the major exception of HPV- smokers, induction chemotherapy followed by surgery with selective CRT is a viable treatment option for tonsil cancer. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1206-1211, 2020.

Transfeminine Gender Confirmation Surgery with Penile Inversion Vaginoplasty: An Initial Experience.

To detail the early experience with and results of a transfeminine (TF) genital reconstruction at an established plastic surgery practice in Western New York. METHODS: Between June 2016 and June 2019, 30 patients underwent penile inversion vaginoplasty for TF gender reassignment. All patients fulfilled World Professional Association for Transgender Health and NY State criteria for reassignment surgery. All surgeries were carried out at a large, government-owned tertiary care center. RESULTS: There were 30 patients in this retrospective study, with a mean age of 37 years (SD 5.4) and a mean body mass index of 27.3 kg/m2 (SD 3.2 kg/m2). Nineteen patients never smoked, 4 were former smokers, and 7 were current smokers. Primary surgery was an orchiectomy and modified single-stage penile inversion vaginoplasty. Mean operative time was 6.0 hours. Mean initial hospital stay was 8.2 days. Three of the 30 (10%) patients required transfusion. There were 6 (20%) complications. Three complications (10%) required reoperation: 1 patient for wound dehiscence on postoperative day 7, 1 for rectal perforation identified on postoperative day 10, and 1 for urethrovaginal fistula. All complications were addressed without sequalae. Twenty of the 30 (66%) patients have undergone revision surgery. Indications for revision were prolapse correction/deepening, labiaplasty, clitoral hood construction/revision, meatal asymmetry, urinary fistula repair, and posterior vaginal flap revision. Twenty-one of 28 (75%) revisions were outpatient surgeries. There were no complications from these procedures. Overall satisfaction via survey was 92% (24 respondents). CONCLUSIONS: TF gender reassignment is a novel, challenging set of procedures for the specialty of plastic surgery. With appropriate consideration and technique, penile inversion vaginoplasty is a safe, effective means of achieving this goal.

Idiosyncrasies of scalp melanoma.

OBJECTIVES/HYPOTHESIS: Examine the accuracy of sentinel lymph node biopsy (SNB) in scalp melanoma (SM), patterns of nodal metastases, patient outcomes, and the utility of immunohistochemistry (IHC) in SNB evaluation. STUDY DESIGN: Retrospective. METHODS: There were 22 patients, 4 females and 18 males. Sentinel lymph nodes (SLN) were localized via preoperative lymphoscintigraphy, intraoperative gamma probe, and Lymphazurin injection. SLNs were stained with hematoxylin-eosin, S-100, HMB-45, Melan-A, micropthalmia transcription factor, and tyrosinase. SLNs were grouped into cervical (levels 1-5) and extracervical (parotid, suboccipital, retroauricular) regions. RESULTS: There were 13 posterior and 9 anterior SMs. The first SNB were mapped to the extracervical regions in 77% of posterior and 78% of anterior lesions. SLN number ranged from 1 to 5. Ten patients had positive SLNs (PSLN). Forty percent of the PSLN group had SLNs mapped in both cervical and extracervical sites. Six underwent completion lymphadenectomy, with no additional positive nodes identified. No significant difference between PSLN and negative sentinel node (NSLN) patients was seen when compared by SLN number, Breslow's thickness, tumor ulceration, and clinical outcomes. Mean follow-up was 35 months. One patient died of disease. One isolated regional recurrence occurred. Sixty percent of PSLN and 92% of NSLN patients were recurrence free at last follow-up. One distant metastasis occurred in the NSLN group, and one local, one regional, and two patients with distant metastases were in the PSLN group at the time of last follow-up. Additional IHC did not detect other metastases in the NSLN group. CONCLUSIONS: SM is aggressive, as demonstrated by the high rate of SLN metastases, and there were no significant histopathologic factors in the primary tumor that predicted the presence of SLN metastases. SNB was accurate. The majority of first SLNs were localized in extracervical basins.

Comparative genomic instabilities of thyroid and colon cancers.

OBJECTIVES: To assess the forms and extent of genomic instability in thyroid cancers and colorectal neoplasms and to determine if such measurements could explain the generally excellent prognosis of thyroid malignant neoplasms compared with colon carcinoma. DESIGN: Tumor genome analyses. Genomic instability was measured by the following 4 methods, listed in ascending order based on the size of events detected: inter-simple sequence repeat polymerase chain reaction (ISSR-PCR), fractional allelic loss (FAL) analysis, array-based comparative genomic hybridization (aCGH), and spectral karyotyping (SKY). RESULTS: The genomic instability index of 32 thyroid carcinomas, 59 colon carcinomas, and 11 colon polyps was determined by ISSR-PCR; no difference was seen among the 3 groups by this method. Fractional allelic loss rates were comparable in thyroid cancers and colon polyps and lower than FAL rates in colorectal cancers. Indolent papillary thyroid carcinomas were essentially diploid with no large-scale alterations in chromosome number or structure when evaluated by aCGH or SKY. In anaplastic thyroid cancers, aCGH revealed abundant chromosome alterations. Colorectal carcinomas showed extensive copy number changes and chromosomal rearrangements when analyzed by aCGH and SKY. CONCLUSIONS: Genomic alterations in papillary thyroid carcinoma, such as in benign colon polyps, are principally smaller events detected by ISSR-PCR. With the more aggressive tumor types (ie, anaplastic thyroid and colorectal carcinomas), larger events detected by FAL analysis, aCGH, and SKY were revealed. We hypothesize that mutations caused by smaller genomic alterations enable thyroid cells to achieve a minimal malignant phenotype. Mutations for aggressive biological behavior appear with larger genomic events.

Intraparotid sentinel lymph node biopsy for head and neck melanoma.

OBJECTIVE: The objective of this retrospective clinical review was to assess the safety and accuracy of intraparotid sentinel node biopsy in patients with melanoma. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Twenty-eight patients with cutaneous melanoma of the head and neck undergoing sentinel lymph node (SLN) biopsy in which the radionuclide localized to the parotid gland on preoperative lymphoscintigraphy were studied. METHODS: All patients underwent wide local excision of the tumor and intraparotid sentinel node biopsy using intraoperative gamma probe localization. RESULTS: There were 25 men and 3 women ranging in age from 34 to 81 years. The primary site was on the auricle in 14 patients: temple, 4; forehead, 5; cheek, 3; and on the neck in 2 patients, respectively. The mean Breslow thickness was 2.3 mm (range, 0.9-7.0 mm). In 27 of 28 patients, an intraparotid SLN was identified. In one patient, final pathology did not reveal lymphoid tissue despite a high count in the parotid tissue excised. Median number of SLN per patient was two. Six patients had microscopic metastases in the SLN. In two of these patients, additional microscopic lymph node metastases were found in the neck after subsequent formal lymphadenectomy. The pathologic staging for the group (n = 14) was: stage 1B, 4; 2A, 4; stage 2B, 3; and stage 3B, 3 patients, respectively. All patients are alive and without evidence of disease (mean follow up, 31 months). There were no surgical complications, specifically no patient experienced temporary or permanent facial paralysis. CONCLUSION: Intraparotid SLN biopsy for staging cutaneous head and neck melanoma is a reliable, accurate, and safe procedure.

Chemoprevention of head and neck cancer with aspirin: a case-control study.

OBJECTIVE: To evaluate the chemopreventive potential of aspirin against head and neck cancer. DESIGN: Hospital-based case-control study. SETTING: National Cancer Institute-designated comprehensive cancer center. Patients Individuals who received medical services at the Roswell Park Cancer Institute, Buffalo, NY, between 1982 and 1998 and who completed a comprehensive epidemiologic questionnaire. MAIN OUTCOME MEASURE: Aspirin use among 529 patients with head and neck cancer and 529 hospital-based control subjects matched by age, sex, and smoking status. RESULTS: Aspirin use was associated with a 25% reduction in the risk of head and neck cancer (adjusted odds ratio, 0.75; 95% confidence interval, 0.58-0.96). Consistent risk reductions were also noted in association with frequent and prolonged aspirin use. Further, a consistently decreasing trend in risk was noted with increasing duration of aspirin use (P(trend) = .005). Risk reduction was observed across all 5 primary tumor sites, with cancers of the oral cavity and oropharynx exhibiting greater risk reduction. When analyzed by smoking and alcohol exposure levels, participants moderately exposed to either showed a statistically significant 33% risk reduction (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.91), whereas participants exposed to both heavy smoking and alcohol use did not benefit from the protective effect of aspirin. The reduction in risk was relatively more significant in women. CONCLUSIONS: Aspirin use is associated with reduced risk of head and neck cancer. This effect is more pronounced in individuals with low to moderate exposure to cigarette smoke or alcohol consumption.

Development of head and neck squamous cell carcinoma is associated with altered cytokine responsiveness.

Growth of head and neck squamous cell carcinoma (HNSCC) is generally associated with an inflammatory component. It is hypothesized that these tumor cells develop mechanisms to evade the growth inhibitory effects of cytokines that are present in the tumor microenvironment. This study determined the changes in responsiveness to inflammatory cytokines that accompany the transition of normal to transformed epithelial cells. Paired primary cultures of normal epithelial cells (NEC) and SCC cells were established from 16 patients. Receptor-mediated activation of signal transducer and activator of transcription and extracellular signal-regulated kinase pathways in response to cytokine treatments was identified by immunoblot analysis. Thymidine incorporation determined the impact of the cytokines on DNA synthesis. HNNEC and HNSCC displayed a prominent signaling in response to oncostatin M, interleukin-6, IFN-gamma, and epidermal growth factor. Untreated HNSCC showed an elevated level of phosphorylated signal transducer and activator of transcription 3 and extracellular signal-regulated kinase (P < 0.001) compared with HNNEC, suggesting constitutively activated pathways. Moreover, HNSCC cells phosphorylated significantly more signal transducer and activator of transcription 1 in response to oncostatin M (P = 0.002) and IFN-gamma (P = 0.018) treatments. DNA synthesis of SCC cells was less inhibited by cytokines produced by endotoxin-stimulated macrophages (P = 0.016) than that of NEC. Low-dose oncostatin M slightly enhanced proliferation of SCC, whereas that of NEC was suppressed (P = 0.016). This study identified significant alterations in signal transduction pathways engaged by cytokines and which are associated with loss of growth inhibition of HNSCC. Increased signal transducer and activator of transcription phosphorylation, along with constitutively phosphorylated extracellular signal-regulated kinase in HNSCC, suggest that these pathways as molecular markers are important in the malignant transformation process and are potential targets for treatment.

Molecular prognosticators and genomic instability in papillary thyroid cancer.

OBJECTIVES/HYPOTHESIS: Tumor progression has been attributed to the accumulation of DNA damage concurrent with selection of advantageous mutations; this DNA damage may result from failure to maintain genomic integrity or from susceptibility to carcinogens. Glutathione S-transferases (GSTs), enzymes that metabolize many carcinogens, may play a role in preserving genome integrity. The objectives of this study are to assess the relationship of GST genotypes with prognosis, clinicopathologic parameters, and genomic instability in papillary thyroid cancer. STUDY DESIGN: Prospective analysis. METHODS: GSTM1 and GSTT1 genotypes of 35 matched normal and papillary thyroid cancer specimens were determined by polymerase chain reaction (PCR) using primers specific for the coding sequences of each gene. Genomic instability was measured by intersimple sequence repeat PCR for each tumor/normal pair and compared with the GAMES prognostic scoring system and clinicopathologic parameters including age, extrathyroidal extension, tumor grade, size, stage metastasis, sex, and smoking history. RESULTS: GSTM1 and GSTT1 null genotypes were found in the normal tissues of 46% and 45%, respectively. No gene losses were detected in the tumor specimens. A significant association between the GSTM1 null genotype and increased risk of recurrence and death was observed. Elevated GII correlated with smoking and tumor stage but not with GST genotype. CONCLUSION: The association of GSTM1 null genotype with intermediate and high risk GAMES categories suggests that GSTM1 provides some protection against disease progression. However, this protection does not confer resistance to disease onset. GST genotyping may be a useful adjunct prognosticator with GAMES.

Advanced soft palate cancer: the clinical importance of the parapharyngeal space.

OBJECTIVE: To identify the incidence of parapharyngeal space (PPS) recurrences and how they impact survival in advanced-stage soft-palate carcinoma patients. STUDY DESIGN AND SETTING: One hundred thirty-seven patients' charts were reviewed from 1971 to 1996. Inclusion criteria were patients who received a per-oral resection, discontinuous neck dissection, and postoperative adjuvant radiation therapy; 15 patients met criteria for inclusion. The incidence of PPS recurrences, regional failure, and survival were endpoints that were analyzed. RESULTS: There were no local failures in our study. Regional failures excluding the PPS (levels I-V) were 27%, and 40% occurred within the PPS. Cervical adenopathy was associated with 83% of the PPS recurrences. Median survival for PPS recurrences was 26 months, compared with 67 months for levels I-V recurrences (n = ns). CONCLUSIONS: The incidence of PPS recurrences is substantial in advanced-stage soft-palate cancer. PPS recurrences negatively impact survival; without effective salvage techniques for these recurrences or effective adjuvant therapy, poor patient outcomes can be expected.

Two Cases of Pneumatosis Intestinalis during Cetuximab Therapy for Advanced Head and Neck Cancer.

Pneumatosis intestinalis is a rare but known potential complication of treatment with cetuximab. Here we present two cases of pneumatosis intestinalis occurring in patients who were receiving cetuximab as treatment for advanced head and neck cancer. In both cases, cetuximab was discontinued after discovery of the pneumatosis intestinalis.

A logical and stepwise operative approach to radical neck dissection.

A thorough understanding of the anatomy of the neck is essential to avoid injury to vital structures when performing radical neck dissection. The complicated anatomical relations of the various nerves, vessels, and muscles within the confined area of the neck can often be daunting. We outline strategic anatomical landmarks and their relationships to important nerves, arteries, veins, and lymphatics to simplify the complicated and formidable anatomy of the neck. We also delineate key maneuvers that, when combined with the anatomical landmarks, offer a stepwise and logical approach to performing radical neck dissection that confers improved safety.

Bronchogenic cyst presenting as a symptomatic neck mass in an adult: case report and review of the literature.

We report the unusual clinical manifestation and subsequent management of a symptomatic congenital bronchogenic cyst that connected to the trachea and presented in the neck of an adult. The embryology, clinical presentation, diagnostic evaluation, and management options of this rare aberration are discussed.

Anaplastic thyroid cancer evolved from papillary carcinoma: demonstration of anaplastic transformation by means of the inter-simple sequence repeat polymerase chain reaction.

BACKGROUND: In thyroid tumors, the coexistence of well- and poorly differentiated tumor types has led to the hypothesis that poorly differentiated thyroid tumors develop from well-differentiated thyroid tumors. By evaluating the genomic instability of histologically distinct but coexisting tumor foci, this study aimed to develop an improved understanding of thyroid tumorigenesis and tumor evolution. DESIGN: Laser capture microdissection (LCM) was carried out on archival formalin-fixed, paraffin-embedded sections from a tumor containing foci of classic papillary thyroid cancer and anaplastic thyroid cancer. DNA was extracted from each microdissected tumor focus. In addition, cryopreserved bulk normal and neoplastic thyroid tissue underwent DNA extraction. All DNA samples were subsequently evaluated for genomic instability by means of inter-simple sequence repeat polymerase chain reaction. RESULTS: The LCM DNA from each archival paraffin-embedded tumor focus demonstrated unique patterns of banding as compared with the cryopreserved tumor and normal tissue DNA. Thus, intratumoral variability in genomic instability was observed. Comparison of inter-simple sequence repeat polymerase chain reaction patterns of LCM DNA from adjacent foci of papillary and anaplastic tumors showed conserved genome alterations. CONCLUSIONS: At the genome level, thyroid tumors may be highly heterogeneous. The intratumoral histologic heterogeneity observed in thyroid neoplasms reflects genetically heterogeneous underlying tumor cell populations that are demonstrated by the observed differences in their rates and extents of genomic instability. The conserved genomic alterations in the microdissected papillary and anaplastic foci suggest intratumoral evolution, with transformation of a preexisting papillary tumor to anaplastic carcinoma.

Current concepts in the management of a second malignancy of the lung in patients with head and neck cancer.

Simultaneous, synchronous, and metachronous presentation of lung malignancies when treating head and neck squamous cell cancers is one of the most difficult challenges in head and neck surgery. However, good (> 40%) 5-year survival can be obtained when proper screening techniques, patient selection, and therapy are combined. Because of the complexity of the head and neck resection and reconstruction and the multiple surgical and medical services used to diagnose and treat this clinical entity, a comprehensive review of the current literature is provided. The clinically pertinent meanings of simultaneous, synchronous, and metachronous second malignancy of the lung are presented. A review of the current literature is presented that divides second lung malignancy into two groups: second primary and metastasis. The incidence of a second lung malignancy is identified. The tools used in the screening of high-risk patients and the role of the new diagnostic studies such as positron emission tomography and positron emission tomography CT scans are reviewed. Finally, the current literature on patient selection and surgical therapy is used to put forth a clinical pathway followed at the authors' institution for the treatment of these patients.

Hypotensive endovascular test occlusion of the carotid artery in head and neck cancer.

OBJECT: To evaluate the reliability of balloon test occlusion with hypotensive challenge (BTO and HC) as a predictor of neurological complications before internal carotid artery (ICA) sacrifice in patients with advanced head and neck cancer, the authors retrospectively reviewed the medical records of patients presenting to their institutions between 1992 and 1997 in whom this preoperative assessment was performed. METHODS: Eleven patents who were candidates for extended comprehensive neck dissection (ECND) and potential ICA sacrifice were included in the study. Eight patients tolerated the test and underwent endovascular occlusion or surgical ligation of the ICA before ECND (four patients), preservation of the ICA at the time of surgery (three patients), or palliative therapy (one patient). Of three patients in whom BTO and HC failed, one patient received palliative treatment only; the other two underwent ECND with preservation of the ICA. In the group of patients who passed the test and underwent ICA occlusion or ligation before ECND, fatal thromboembolic stroke occurred within 24 hours of permanent balloon occlusion in one patient, resulting in a combined neurological morbidity/mortality rate of 25% in this subset of patients and an overall complication rate of 9% in this series. CONCLUSIONS: The authors found that BTO and HC offers a simple and reliable method of preoperative risk assessment when ICA resection is planned for regional control of disease in advanced head and neck cancer. This management option, however, is associated with a potential for neurological complication that must be weighed against the natural course of the disease and the risks and benefits of other treatment modalities.

Adenoid cystic carcinoma of the paranasal sinuses or nasal cavity: a 40-year review of 35 cases.

We retrospectively reviewed 35 cases of adenoid cystic carcinoma that had originated in the minor salivary glands of the paranasal sinuses or nasal cavity. All patients had been seen at two tertiary-care referral centers in western New York State between 1960 and 2000. Twenty patients had been treated with surgery and adjuvant radiotherapy, 10 patients with surgery alone, three with radiotherapy alone, and two with concurrent radiotherapy and chemotherapy. During the study, 22 patients developed recurrent disease--11 locally; three distantly; seven locally and distantly; and one locally, regionally, and distantly. At the conclusion of the study, 14 patients were alive and disease-free, and eight were alive with disease; 10 patients had died with disease, and three had died of other causes with no evidence of disease. Adenoid cystic carcinoma of the paranasal sinuses or nasal cavity is an aggressive neoplasm that results in a high incidence of both local recurrence and distant metastasis, regardless of treatment modality. Most cases are ultimately fatal, although long disease-free intervals have been observed. A combination of surgery and radiotherapy offers these patients the best chance for disease control.