Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, introduces significant modifications from the prior seventh edition. This article details several of the most significant modifications, and the rationale for the revisions, to alert the reader to evolution of the field. The most significant update creates a separate staging algorithm for high-risk human papillomavirus-associated cancer of the oropharynx, distinguishing it from oropharyngeal cancer with other causes. Other modifications include: the reorganizing of skin cancer (other than melanoma and Merkel cell carcinoma) from a general chapter for the entire body to a head and neck-specific cutaneous malignancies chapter; division of cancer of the pharynx into 3 separate chapters; changes to the tumor (T) categories for oral cavity, skin, and nasopharynx; and the addition of extranodal cancer extension to lymph node category (N) in all but the viral-related cancers and mucosal melanoma. The Head and Neck Task Force worked with colleagues around the world to derive a staging system that reflects ongoing changes in head and neck oncology; it remains user friendly and consistent with the traditional tumor, lymph node, metastasis (TNM) staging paradigm. CA Cancer J Clin 2017;67:122-137. © 2017 American Cancer Society.

Elective neck dissection (END) and cN0 hard palate and upper gingival cancers: A National Cancer Database analysis of factors predictive of END and impact on survival.

BACKGROUND AND OBJECTIVES: The reported risk of nodal metastasis in hard palate and upper gingival squamous cell carcinoma (SCC) has been inconsistent with inadequate consensus regarding the utility of neck dissection in the clinically negative (cN0) neck. MATERIALS AND METHODS: Using the National Cancer Database, cN0 patients diagnosed with SCC of the head and neck with the subsites of the hard palate and upper gingiva were identified from 2004 to 2014. RESULTS: A total of 1830 patients were identified, and END was performed on 422 patients with cN0 tumors. Pathologically positive nodes occurred in 14% (59/422) of patients in this cohort. Higher tumor stage, academic hospital type, and large hospital volume (>28 cancer-specific cases/year) were associated with a higher likelihood of END both in univariate and multivariate analyses (P < .05). Patients >80 years of age were less likely to receive END on multivariate analysis (OR 0.52, 0.32-0.84). No variables, including advanced T stage, predicted occult metastases. Cox proportional hazards regression analysis showed that patients who underwent END demonstrated improved OS over an 11-year period (hazard ratio 0.75, P = .002). On subgroup analysis, this improvement was significant in patients with both stage T1 and T4 tumors. CONCLUSIONS: Tumor stage, hospital type, and hospital volume were associated with higher rates of END for patients with cN0 hard palate SCC and after controlling for clinical factors, END was associated with improved overall survival.

Feasibility of a Video-Mosaicking Approach to Extend the Field-of-View For Reflectance Confocal Microscopy in the Oral Cavity In Vivo.

BACKGROUND: Reflectance confocal microscopy (RCM) is a developing approach for noninvasive detection of oral lesions with label-free contrast and cellular-level resolution. For access into the oral cavity, confocal microscopes are being configured with small-diameter telescopic probes and small objective lenses. However, a small probe and objective lens allows for a rather small field-of-view relative to the large areas of tissue that must be examined for diagnosis. To extend the field-of-view for intraoral RCM imaging, we are investigating a video-mosaicking approach. METHODS: A relay telescope and objective lens were adapted to an existing confocal microscope for access into the oral cavity. Imaging was performed using metal three-dimensional-printed objective lens front-end caps with coverslip windows to contact and stabilize the tissue and set depth. Four healthy volunteers (normal oral mucosa), one patient (with an amalgam tattoo) in a clinical setting, and 20 anesthetized patients (with oral squamous cell carcinoma [OSCC]) in a surgical setting were imaged. Instead of the usual still RCM images, videos were recorded and then processed into video-mosaics. Thirty video-mosaics were read and qualitatively assessed by an expert reader of RCM images of the oral mucosa. RESULTS: Whereas the objective lens' native field-of-view is 0.75 mm × 0.75 mm, the video-mosaics display larger areas, ranging from 2 mm × 2 mm to 4 mm × 2 mm, with resolution, morphologic detail, and image quality that is preserved relative to that observed in the original videos (individual images). Video-mosaics in healthy volunteers' and the patients' images showed cellular morphologic patterns in the lower epithelium and at the epithelial junction, and connective tissue along with capillary loops and blood flow in the deeper lamina propria. In OSCC, tumor nests could be observed along with normal looking mucosa in margin areas. CONCLUSIONS: Video-mosaicking is a reasonably quick and efficient approach for extending the field-of-view of RCM imaging, which can, to some extent, overcome the inherent limitation of an intraoral probe's small field-of-view. Reading video-mosaics can mimic the procedure for examining pathology: initial visualization of the spatial cellular and morphologic patterns of the tumor and the spread of tumor margins over larger areas of the lesion, followed by digitally zooming (magnifying) for closer inspection of suspicious areas. However, faster processing of videos into video-mosaics will be necessary, to allow examination of video-mosaics in real-time at the bedside. Lasers Surg. Med. 51:439-451, 2019. © 2019 Wiley Periodicals, Inc.

Factors associated with a primary surgical approach for sinonasal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Primary surgery is the preferred treatment of T1-T4a sinonasal squamous cell carcinoma (SNSCC). METHODS: Patients with SNSCC in the National Cancer Data Base (NCDB) were analyzed. Factors that contributed to selecting primary surgical treatment were examined. Overall survival (OS) in surgical patients was analyzed. RESULTS: Four-thousand seven hundred and seventy patients with SNSCC were included. In T1-T4a tumors, lymph node metastases, maxillary sinus location, and treatment at high-volume centers were associated with selecting primary surgery. When primary surgery was utilized, tumor factors and positive margin guided worse OS. Adjuvant therapy improved OS in positive margin resection and advanced T stage cases. CONCLUSIONS: Tumor and non-tumor factors are associated with selecting surgery for the treatment of SNSCC. When surgery is selected, tumor factors drive OS. Negative margin resection should be the goal of a primary surgical approach. When a positive margin resection ensues, adjuvant therapy may improve OS.

Prognostic value of FDG-PET prior to autologous stem cell transplantation for relapsed and refractory diffuse large B-cell lymphoma.

High-dose chemotherapy (HDT) plus autologous stem cell transplantation (ASCT) is the standard of care for chemosensitive relapsed and refractory diffuse large B-cell lymphoma (rel/ref DLBCL). Interim restaging with functional imaging by positron emission tomography using (18)F-deoxyglucose (FDG-PET) has not been established after salvage chemotherapy (ST) and before HDT-ASCT by modern criteria. Herein, we evaluated 129 patients with rel/ref DLBCL proceeding to HDT-ASCT, with ST response assessment by FDG-PET according to the contemporary Deauville 5-point scale. At 3 years, patients achieving a Deauville response of 1 to 3 to ST experienced superior progression-free survival (PFS) and overall survival (OS) rates of 77% and 86%, respectively, compared with patients achieving Deauville 4 (49% and 54%, respectively) (P < .001). No other pre-HDT-ASCT risk factors significantly impacted PFS or OS. Despite achieving remission to ST, patients with Deauville 4 should be the focus of risk-adapted investigational therapies.

Management and outcome of clinically evident neck recurrence in patients with papillary thyroid cancer.

BACKGROUND: The aim of this study was to report our incidence of clinically evident neck recurrence, salvage neck management and subsequent outcomes in patients with papillary thyroid cancer. This is important to know so that patients with thyroid cancer can be properly counselled about the implications of recurrent disease and subsequent outcome. METHODS: An institutional database of 3664 patients with thyroid cancer operated between 1986 and 2010 was reviewed. Patients with nonpapillary histology and gross residual disease and those with distant metastases at presentation or distant metastases prior to nodal recurrence were excluded from the study. Of these, 99 (3.0%) patients developed clinically evident nodal recurrence. Details of recurrence and subsequent therapy were recorded for each patient. Subsequent disease-specific survival (sDSS), distant recurrence-free survival (sDRFS) and nodal recurrence-free survival (sNRFS) were determined from the date of first nodal recurrence using the Kaplan-Meier method. RESULTS: Of the 99 patients, 59% were female and 41% male. The median age was 41 years (range 5-91). The majority of patients had pT3/4 primary tumours (63%) and were pN+ (78%) at initial presentation. The median time to clinically evident nodal recurrence was 28 months (range: 3-264). Nodal recurrence occurred in the central neck in 15 (15%) patients, lateral neck in 74 (75%) patients and both in 10 (10%) patients. After salvage treatment, the 5-year sDSS was 97.4% from time of nodal recurrence. The 5-year sDRFS and sNRFS were 89.2% and 93.7%, respectively. CONCLUSION: In our series, isolated clinically evident nodal recurrence occurred in 3.0% of patients. Such patients are successfully salvaged with surgery and adjuvant therapy with sDSS of 97.4% at 5 years.

The potential benefit of allogeneic over autologous transplantation in patients with very early relapsed and refractory follicular lymphoma with prior remission duration of ≤12 months.

Early relapsed or refractory follicular lymphoma (FL) warrants consolidation with transplantation, though graft source modality remains controversial. We analysed the outcomes of 44 patients transplanted with either autologous or allogeneic graft sources in the post-rituximab era. No difference in event-free (EFS) or overall survival (OS) was observed between allogeneic (81% and 81%) and autologous transplantation (64% and 70%) at 3 years. There was a significant difference in EFS between allogeneic and autologous transplantation patients with previous remission duration of ≤12 months (80% and 42% at 3 years, P < 0·015). Very early relapsed FL may warrant consideration of allogeneic over autologous transplantation in the appropriate setting.

Role of RAI in the management of incidental N1a disease in papillary thyroid cancer.

BACKGROUND: Following total thyroidectomy (TT) for papillary thyroid cancer (PTC), pathological assessment can occasionally reveal incidental perithyroidal lymph nodes (LNs) with occult metastases. These cN0pN1a patients often receive radioactive iodine (RAI) therapy for this indication alone. The aim of this study was to determine the central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. METHODS: An institutional database of 3664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010 was reviewed. A total of 232 pT1-3 patients managed with TT and no neck dissection were subsequently found to have incidental level 6 LNs on pathology. Patients with other indications for RAI, such as extrathyroidal extension and close or positive margins, were excluded. One hundred and four patients remained for analysis. Kaplan-Meier method was used to determine central neck LN recurrence-free survival (RFS). RESULTS: The median age of the cohort was 40 years (range 17-83). The median follow-up was 53 months (range 1-211). The median number of positive LNs removed and maximum LN diameter were 1 (range 1-8) and 5 mm (range 1-16 mm), respectively. A total of 67 (64%) patients had adjuvant RAI and 37 (36%) did not. Patients with vascular invasion (P = 0·01), LNs >2 mm (P = 0·07) and >2 positive nodes (P = 0·06) were more likely to be selected for adjuvant RAI therapy. Patients without RAI therapy had similar 5-year central neck LN RFS compared to those treated with RAI: 96·2% vs 94·6%, respectively (P = 0·92). CONCLUSION: There is no difference in the 5-year central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment.

Definition of bulky disease in early stage Hodgkin lymphoma in computed tomography era: prognostic significance of measurements in the coronal and transverse planes.

Disease bulk is an important prognostic factor in early stage Hodgkin lymphoma, but its definition is unclear in the computed tomography era. This retrospective analysis investigated the prognostic significance of bulky disease measured in transverse and coronal planes on computed tomography imaging. Early stage Hodgkin lymphoma patients (n=185) treated with chemotherapy with or without radiotherapy from 2000-2010 were included. The longest diameter of the largest lymph node mass was measured in transverse and coronal axes on pre-treatment imaging. The optimal cut off for disease bulk was maximal diameter greater than 7 cm measured in either the transverse or coronal plane. Thirty patients with maximal transverse diameter of 7 cm or under were found to have bulk in coronal axis. The 4-year overall survival was 96.5% (CI: 93.3%, 100%) and 4-year relapse-free survival was 86.8% (CI: 81.9%, 92.1%) for all patients. Relapse-free survival at four years for bulky patients was 80.5% (CI: 73%, 88.9%) compared to 94.4% (CI: 89.1%, 100%) for non-bulky; Cox HR 4.21 (CI: 1.43, 12.38) (P=0.004). In bulky patients, relapse-free survival was not impacted in patients treated with chemoradiotherapy; however, it was significantly lower in patients treated with chemotherapy alone. In an independent validation cohort of 38 patients treated with chemotherapy alone, patients with bulky disease had an inferior relapse-free survival [at 4 years, 71.1% (CI: 52.1%, 97%) vs 94.1% (CI: 83.6%, 100%), Cox HR 5.27 (CI: 0.62, 45.16); P=0.09]. Presence of bulky disease on multidimensional computed tomography imaging is a significant prognostic factor in early stage Hodgkin lymphoma. Coronal reformations may be included for routine Hodgkin lymphoma staging evaluation. In future, our definition of disease bulk may be useful in identifying patients who are most appropriate for chemotherapy alone.

Central nervous system involvement in T-cell lymphoma: A single center experience.

Background We characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T-cell lymphoma (PTCL). Methods Retrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994-2011 with a minimum six months of follow-up or an event defined as relapse or death. Results Histologies included peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B-cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16-103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III-IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10-75). Conclusions Despite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥3.

Very low utility of surveillance imaging in early-stage classic Hodgkin lymphoma treated with a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine and radiation therapy.

BACKGROUND: This study evaluated the need for surveillance imaging in early-stage classic Hodgkin lymphoma (cHL) after planned combined-modality therapy (CMT). METHODS: Primary early-stage cHL patients who underwent CMT were included. Positron emission tomography (PET)/computed tomography (CT), CT, or both were performed at the initial staging, during or after chemotherapy, and for at least 2 years during follow-up. Imaging studies and medical records were reviewed to determine if and when relapse had occurred. Radiation doses and costs were also calculated from follow-up imaging. RESULTS: The study included 78 patients with a median follow-up of 46 months; 85% of the patients had stage II disease (32% with bulky disease). Four of 77 interim PET scans were positive; none of these patients relapsed during follow-up, which ranged from 24 to 80 months. After a total of 466 follow-up imaging studies (91% with CT and 9% with PET/CT), no cHL relapse was detected. Eleven abnormal findings were noted on surveillance imaging: 9 were false-positives, and 2 were second primary malignancies. The average cumulative dose per patient from follow-up imaging was 107 mSv, which translated into an estimated lifetime excess cancer risk of 0.5%; the estimated total costs were $296,817 according to Medicare reimbursements. CONCLUSIONS: Surveillance imaging with either CT or PET/CT can be omitted safely for early-stage cHL treated with a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine and radiation therapy because the risk of relapse is extremely low. This observation also applies to patients with bulky disease. The elimination of surveillance imaging will also reduce healthcare expenses and cumulative radiation doses in these predominantly young patients.

Cost-effectiveness analysis of papillary thyroid cancer surveillance.

BACKGROUND: The recent overdiagnosis of subclinical, low-risk papillary thyroid cancer (PTC) coincides with a growing national interest in cost-effective health care practices. The aim of this study was to measure the relative cost-effectiveness of disease surveillance of low-risk PTC patients versus intermediate- and high-risk patients in accordance with American Thyroid Association risk categories. METHODS: Two thousand nine hundred thirty-two patients who underwent thyroidectomy for differentiated thyroid cancer between 2000 and 2010 were identified from the institutional database; 1845 patients were excluded because they had non-PTC cancer, underwent less than total thyroidectomy, had a secondary cancer, or had <36 months of follow-up. In total, 1087 were included for analysis. The numbers of postoperative blood tests, imaging scans and biopsies, clinician office visits, and recurrence events were recorded for the first 36 months of follow-up. Costs of surveillance were determined with the Physician Fee Schedule and Clinical Lab Fee Schedule of the Centers for Medicare and Medicaid Services. RESULTS: The median age was 44 years (range, 7-83 years). In the first 36 months after thyroidectomy, there were 3, 44, and 22 recurrences (0.8%, 7.8%, and 13.4%) in the low-, intermediate-, and high-risk categories, respectively. The cost of surveillance for each recurrence detected was US $147,819, US $22,434, and US $20,680, respectively. CONCLUSIONS: The cost to detect a recurrence in a low-risk patient is more than 6 and 7 times greater than the cost for intermediate- and high-risk PTC patients. It is difficult to justify this allocation of resources to the surveillance of low-risk patients. Surveillance strategies for the low-risk group should, therefore, be restructured.

Excellent outcomes and lack of prognostic impact of cell of origin for localized diffuse large B-cell lymphoma in the rituximab era.

Therapeutic options for limited-stage diffuse large B cell lymphoma (DLBCL) include short- or full-course R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) ± radiotherapy. The optimal treatment remains unclear. The prognostic value of cell-of-origin (COO) in early stage DLBCL is unknown. Patients with limited-stage DLBCL (stage I or stage II, non-bulky) treated with R-CHOP ± involved field radiotherapy (IFRT) from 1999 to 2012 were included. COO by the Hans algorithm was analysed in a subset of patients. Of 261 patients, 30% were stage I (N = 82), 37% stage IE (N = 96), <1% stage IXEE (N = 1), 18% stage II (N = 46) and 14% stage IIE (N = 37). The stage-modified International Prognostic Index stratified patients into prognostically relevant groups. There was no significant difference in progression-free survival (PFS) or overall survival (OS) for patients in the germinal centre B-cell-like (GCB; n = 65) and non-GCB cohorts (n = 22). Seventeen patients received R-CHOP × 3-4 cycles (Arm A), 147 received R-CHOP × 3-4 cycles + IFRT (Arm B), 48 received R-CHOP × 6 cycles (Arm C), and 50 received R-CHOP × 6 cycles + IFRT (Arm D). The outcomes were excellent, with 5-year PFS of 82% and 5-year OS of 93%, and were similar across the 4 treatment groups. In the rituximab era, outcomes for limited-stage DLBCL, regardless of treatment approach, were excellent. Baseline COO was not a significant prognostic factor in patients treated with short-course R-CHOP + IFRT.

Survival outcomes after treatment of cancer of the oral cavity (1985-2015).

OBJECTIVES: To present treatment results of oral squamous cell carcinoma (OSCC) at a tertiary cancer care center from 1985 to 2015. MATERIALS AND METHODS: A total of 2082 patients were eligible for this study. Main outcomes measured were overall survival (OS) and disease specific survival (DSS). Prognostic variables were identified with bivariate analyses using Kaplan-Meier curves and log-rank testing for comparison. A p-value < 0.05 was considered statistically significant and significant factors were entered into multivariate analysis. Median age was 62 years (16-100), 56% were men, 66% reported a history of tobacco use and 71% of alcohol consumption. The most common subsite was tongue (51%). Seventy-three percent of patients had cT1-2 and 71% had clinically negative necks (cN0). Surgery alone was performed in 1348 patients (65%), adjuvant postoperative radiotherapy in 608 patients (29%) and postoperative chemoradiation in 126 patients (6%). Neck dissection was performed in 920 patients with cN0, and in 585 patients with a clinically involved neck. The median follow-up was 37.6 months (range 1-382). RESULTS: The 5-year OS and DSS were 64.4% and 79.3%, respectively. Age, comorbidities, margin status, vascular invasion, perineural invasion, AJCC 8th edition pT, and pN were independent prognostic factors of OS (p < 0.05). History of alcohol consumption, margin status, vascular invasion, perineural invasion, pT, and pN were independent prognostic factors of DSS (p < 0.05). CONCLUSION: pN stage is the most powerful and consistent predictor of outcome in patients with OSCC treated with primary surgery and appropriate adjuvant therapy.

Stage migration with the new American Joint Committee on Cancer (AJCC) staging system (8th edition) for differentiated thyroid cancer.

BACKGROUND: Tumor, node, and metastasis staging in thyroid carcinoma is important for assessing prognosis. However, patients with stage III or IV disease have an overall survival rate of 90%. The change to 55 years of age as the cutoff will create stage migration and many patients will be downstaged. METHODS: We reviewed our database of 3,650 patients to analyze the impact of the new American Joint Committee on Cancer staging system. There were 994 men (27%) and 2,656 women (73%). The median age was 46 years. Patients were staged using both 7th and 8th editions, with a cutoff of 55 years of age and new definitions of T3 and T4, and nodal staging. RESULTS: Of 3,650 patients, 1,057 (29%) were downstaged. There were 104 (10%) who went from stage IV to I, 109 (10%) who went from stage IV to stage II, and 68 (6%) who went to stage III. There were 218 (21%) who went from stage III to I, 347 (33%) who went from stage III to stage II, and 211 (20%) who went from stage II to I. The overall disease-specific and relapse-free survival was analyzed and showed better stratification with the new staging system. CONCLUSION: The new staging system reflects more appropriately the biology of thyroid cancer and will have significant impact on the management of thyroid cancer.

Do we need a different staging system for tongue and gingivobuccal complex squamous cell cancers?

OBJECTIVES: To determine the need for a separate staging system for gingivobuccal complex squamous cell cancers (GBCSCC) based on 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) data from one institution. PATIENTS AND METHODS: An Institutional Review Board (IRB)-approved retrospective analysis was performed on an oral cavity cancer patient database. Patients from 1985 to 2012 with primary surgical treatment for biopsy-proven squamous cell cancer (SCC) from either the oral tongue (TSCC Group) or gingivobuccal complex (GBCSCC Group), were selected as two separate subgroups. The clinicopathologic data were used to stage the patients based on the American Joint Committee on Cancer 7th edition. Survival outcomes including 5-year OS, RFS, and DSS were calculated and analyzed. A multivariate analysis was performed to identify if subsite was an independent predictor for the survival outcomes, adjusting for other variables. A p-value of less than .05 was considered statistically significant. RESULTS: 936 patients with TSCC and 486 patients with GBCSCC were considered eligible for the analysis. Patients with GBCSCC were more likely to be older (p < .001) and presented with more advanced disease (p < .001) compared to patients with TSCC. Unadjusted hazard ratio (HR) suggested GBCSCC had poor OS compared to TSCC. However, after adjusting for other variables, the adjusted HR was not significant (p = .593). There was no difference in 5-year DSS or RFS in either of the study groups. CONCLUSION: With similar survival outcomes by stage, there is no justification for using a different staging system for GBCSCC.

Neck recurrence in clinically node-negative oral cancer: 27-year experience at a single institution.

OBJECTIVES: Neck failure in patients with oral squamous cell carcinoma (OSCC) carries a poor outcome, yet the management of patients who initially present with clinically node-negative (cN0) neck is not clearly defined. PATIENTS AND METHODS: Retrospective review of patients with cN0 OSCC treated at Memorial Sloan Kettering Cancer Center from 1985 to 2012, focusing on rate, pattern and predictors of neck failure, salvage treatment, and survival outcomes. RESULTS: Of 1,302 patients, 806 (62%) underwent elective neck dissection (END) and 496 (38%) had observation. 190 patients (15%) developed neck recurrence. Median follow-up was 58.5 months (range 1-343); 5-year neck recurrence-free survival (NRFS) was 85% and 80% for the END and observation group respectively (p = .06). Patients with neck failure had poorer outcomes than patients without neck failure (5-year overall survival, 37% vs. 74% [p < .001]; disease-specific survival [DSS], 41% vs. 91% [p < .001]). Independent predictors of neck failure were smoking, primary tumor subsite (hard palate and upper gum), and extranodal extension. 87% of patients underwent salvage treatment (END: 81.1%; observation: 94%). Salvage surgery with adjuvant (chemo) radiation had better DSS than surgery alone or nonsurgical salvage. CONCLUSIONS: In our cohort of patients with initially cN0 OSCC triaged to END vs. observation using clinical parameters, 15% developed neck failure. Salvage treatment was feasible in most cases but survival was poorer compared to patients without neck failure. Surgery followed by adjuvant (chemo) radiation resulted in the best outcome.

Patterns of recurrence in oral tongue cancer with perineural invasion.

BACKGROUND: Although perineural invasion (PNI) is recognized as an adverse prognostic factor in oral tongue squamous cell carcinoma (SCC), the patterns of failure are poorly defined. METHODS: Patients with oral tongue SCC who received primary surgical treatment were identified. Specimens were reviewed by head and neck pathologists. Disease-specific survival (DSS) and locoregional recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant recurrence-free survival (DRFS) were calculated. The PNI and PNI characteristics were analyzed as predictors of outcome. The utility of grading the extent of PNI was assessed by quantifying the number of PNI foci per slide reviewed, nerve caliber, and percent circumference involved. RESULTS: Patients with PNI had a decreased DSS; however, PNI was not predictive of LRFS or RRFS. Patients with PNI were more likely to develop a distant recurrence and 19.40 (confidence interval [CI] 6.70-56.14; P < .001) times more likely to develop a distant recurrence if PNI foci density was >1. CONCLUSION: The presence of PNI in oral tongue SCC predicts worse DSS, with distant recurrence as the most common pattern of failure. High PNI foci density is associated with worse DRFS.

Influence of bone invasion on outcomes after marginal mandibulectomy in squamous cell carcinoma of the oral cavity.

INTRODUCTION: Marginal mandibulectomy (MM) is indicated for oral cavity squamous cell carcinomas (OCSCC) that abut or minimally erode the mandible without gross invasion. Successful implementation of MM is predicated on accurate patient selection and appropriate adjuvant treatment based on well-known host and tumor characteristics. The incidence of microscopically diagnosed bone involvement in MM specimens and its implications on outcomes have however not been reported in large contemporary series. PURPOSE: To report the incidence of bone involvement and analyze its influence on oncologic outcomes in selected patients who underwent MM in treatment of OCSCC. METHOD: A retrospective cohort study was performed on a consecutive series of previously untreated patients requiring MM, at a tertiary care cancer center, between 1985 and 2012 (n = 326). The median age was 64 years and 59% were male. The majority of patients (67%) had a primary tumor of the floor of the mouth or lower alveolus, 80% were clinically staged T1-2, and 31% were clinically N+. Postoperative radiation (PORT) was used in 27% and chemoradiation (POCTRT) in 8% of patients who had microscopic bone invasion. The median follow up period was 55 months and endpoints of interest were local and regional recurrence free (LRFS and RRFS) and disease specific (DSS) survival. RESULTS: Microscopic bone invasion was present in 15% of patients (n = 49). Among these, cortical invasion was present in 32, medullary in 13, and it was not specified in 4. Eight patients had microscopic positive bone margins. Positive bone margins were associated with medullary bone involvement (p < 0.001), floor of mouth and buccal mucosa primary site (p = 0.03), and positive soft tissue margins (p = 0.06). LRFS and DSS were similar in patients without versus with bone invasion (62.8% vs 79.7% and 76.2% vs 66% respectively, p = NS). LRFS were similar in patients with microscopic positive versus negative bone margins, as long as postoperative adjuvant treatment was administered. CONCLUSION: Microscopic bone involvement does not adversely influence outcomes but medullary bone involvement does confer a higher risk of positive bone margins. MM and appropriate adjuvant treatment is an effective strategy for treatment of OCSCC in selected patients with primary tumors adherent to or in proximity to the mandible.

A Proposal to Redefine Close Surgical Margins in Squamous Cell Carcinoma of the Oral Tongue.

Importance: Resection of the primary tumor with negative margins is the gold standard treatment for squamous cell carcinoma of the oral tongue (SCCOT). A microscopically positive surgical margin is clearly associated with a higher risk for local recurrence, whereas a negative margin has traditionally been defined as greater than 5.0 mm clearance from the tumor, with lesser margins arbitrarily designated as close. The precise cutoff at which the risk for local recurrence with a close margin approximates that of a microscopically positive margin remains unclear. Objective: To determine whether the arbitrarily defined close margin (<5.0 mm) would portend as high a risk for local recurrence as a positive margin after resection of SCCOT. Design, Setting, and Participants: In this retrospective study, head and neck pathologists reviewed archived tumor specimens from 381 patients with SCCOT who underwent primary surgical resection at a tertiary care center from January 1, 2000, through December 31, 2012. Data were analyzed from November 15, 2015, to January 5, 2016. Time-dependent receiver operating characteristic curve analysis was used in patients who did not have a microscopically positive margin to determine an optimal margin cutoff for local recurrence-free survival (LRFS). Pathologic factors were assessed for LRFS in a multivariate Cox proportional hazards regression model. Main Outcomes and Measures: The primary end point was evaluation of the margin distance associated with LRFS. Results: Among the 381 patients included in the analysis (222 men [58.3%] and 159 women [41.7%]; mean [SD] age, 58 [14.7] years), the optimal cutoff associated with LRFS was determined to be 2.2 mm. This cutoff was compared with the traditionally accepted cutoff of 5.0 mm. Patients with a margin of 2.3 to 5.0 mm had similar LRFS as patients with a margin of greater than 5.0 mm (hazard ratio [HR], 1.31; 95% CI, 0.58-2.96), and all other comparisons were significantly different (HR for positive margin, 9.03; 95% CI, 3.45-23.67; HR for 0.01- to 2.2-mm margin, 2.83; 95% CI, 1.32-6.07). Based on this result, negative margins were redefined as those with a clearance of greater than 2.2 mm. In a multivariate model adjusting for pathologic factors, positive margins (adjusted HR, 5.73; 95% CI, 2.45-13.41) and margins of 0.01 to 2.2 mm (adjusted HR, 2.00; 95% CI, 1.13-3.55) were the variables most significantly associated with LRFS. Conclusions and Relevance: In this study, local recurrence-free survival was significantly affected only with surgical margins of less than or equal to 2.2 mm in patients with SCCOT. This new definition of close margins stratifies the risk for local recurrence better than the arbitrary 5.0-mm cutoff that has been used.