Osseous Maxillary Reconstruction with Immediate Dental Implant Placement: An Optimized Workflow for the Oncologic Patient.

INTRODUCTION: Maxillary reconstruction is a complex undertaking characterized by a 3-dimensional surgical site with deficiencies in multiple tissue types. Prior to virtual surgical planning(VSP), bony reconstruction was inaccurate and inefficient, thus reconstructions defaulted to soft tissue flaps or obturators. The current study describes an efficient and accurate approach to bony maxillary reconstruction with immediate dental implant placement(IDIP). METHODS: A reconstructive workflow was developed for osseous reconstruction to improve functional and aesthetic outcomes. Critical aspects include VSP, 3-D printed plates and IDIP. Review of a prospectively maintained database identified patients who underwent osseous maxillary reconstruction with a fibula flap and immediate dental implants from 2017-2022, with a focus on oncologic characteristics and reconstructive outcomes. RESULTS: During the study, 20 patients underwent maxillary reconstruction with VSP and IDIP. One dental implant out of 55 failed to osseointegrate and no flaps were lost. Three patients suffered partial loss of the fibula skin island; one required palatal closure with a radial forearm flap, and two were managed with outpatient debridement. Fifteen patients achieved either an interim or final retained dental prosthesis. All prostheses achieved acceptable aesthetic results without the instability associated with non-bone borne devices(e.g.dentures/obturators). No patients experienced delays in oncologic treatment. CONCLUSIONS: VSP technology has enabled surgeons to replace like with like to achieve better outcomes with acceptable morbidity for maxillary defects. IDIP provides all patients an opportunity for a fixed prosthesis even though not all complete the process. This maxillary reconstruction workflow can be safely accomplished in oncologic patients with promising and effective early results.

Long-term regional control and survival in patients with "low-risk," early stage oral tongue cancer managed by partial glossectomy and neck dissection without postoperative radiation: the importance of tumor thickness.

BACKGROUND: The objectives of this study were to determine the incidence of locoregional failure in patients with low-risk, early stage oral tongue squamous cell cancer (OTSCC) who undergo partial glossectomy and ipsilateral elective neck dissection without receiving postoperative radiation. METHODS: A combined database of patients with OTSCC who received treatment at Memorial Sloan-Kettering Cancer Center and Princess Margaret Cancer Center from 1985 to 2005 was established. In total, 164 patients with pathologic T1-T2N0 OTSCC who underwent partial glossectomy and ipsilateral elective neck dissection without postoperative radiation were identified. Patient-related, tumor-related, and treatment-related characteristics were recorded. Local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were calculated by the Kaplan-Meier method. Predictors of outcome were analyzed by univariate and multivariate analysis. RESULTS: At a median follow-up of 66 months (range 1-171 months), the 5-year rates of local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were 89%, 79.9%, and 85.6%, respectively. Regional recurrence was ipsilateral in 61% of patients and contralateral in 39% of patients. The regional recurrence rate was 5.7% for tumors <4 mm and 24% for tumors ≥ 4 mm. Multivariate analysis indicated that tumor thickness was the only independent predictor of neck failure (regional recurrence-free survival, 94% vs 72% [P = .02] for tumors <4 mm vs ≥ 4 mm, respectively). Patients who developed recurrence in the neck had a significantly poorer disease-specific survival compared with those who did not (33% vs 97%; P < .0001). CONCLUSIONS: Patients with low-risk, pathologic T1-T2N0 OTSCC had a greater than expected rate of neck failure, with contralateral recurrence accounting for close to 40% of recurrences. Failure occurred predominantly in patients who had primary tumors that were ≥ 4 mm thick.

Making the Case for Virtual Surgical Planning: Bilateral Sequential Fibula Flaps with Immediate Dental Implants for Maxillectomy.

SUMMARY: Oncologic maxillectomy defects requiring bony reconstruction are among the most challenging head and neck cases because of the complex three-dimensional geometry of the midface. Virtual surgical planning technology is advantageous in these cases because it provides superior positional precision and accuracy compared with traditional techniques and facilitates prosthodontic rehabilitation. Maxillary cancer recurrence after an initial fibula flap reconstruction presents a unique challenge. The authors report the first two cases of sequential fibula flaps after second or recurrent cancer of the maxilla. Virtual surgical planning facilitated resection with adequate tumor margins, optimized anatomic positioning of the fibula construct with three-dimensional printed plates, and enabled immediate functional dental implant placement.

Polyethylene Glycol 3350 (PEG 3350) as a Practical Vehicle for Rapid Reconstitution of PARPi-FL Formulations for Clinical Use.

PARPi-FL is a molecularly specific fluorescent agent that targets poly ADP-ribose polymerase 1, a DNA repair enzyme overexpressed in the nuclei of tumor cells. This imaging agent is being investigated in a clinical trial (NCT03085147) for the detection of oral cancer. The PARPi-FL mouthwash formulation currently being used in the phase I/II clinical trial comprises 1,000 nM of PARPi-FL dissolved first in 4.5 ml of polyethylene glycol (PEG) 300 and then in 9.5 ml of water. This formulation requires a 2-step process that can be cumbersome for routine clinical use. To minimize errors and simplify the formulation process, we have developed a new one-step formulation, which requires only the direct addition of water into a vial containing a mixture of the PARPi-FL and PEG 3350, which is also a powder. In a series of analytical and preclinical studies, we demonstrate that the new formulation of PARPi-FL is stable over 365 days, sustains its characteristics, and performs similar to the previous formulation. Moving forward, the new formulation of the PARPi-FL will be used for patients accrued in the phase II clinical trial.

Clinicopathologic Characteristics of Young Patients with Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) occasionally occurs in young patients and is likely to be distinct from OSCC in older patients. In this retrospective study, we described the clinicopathologic features and outcome of 150 OSCCs that were diagnosed in patients 40-year-old or younger. Most patients (63%) were non-smokers. The most common site of the primary tumor was oral tongue (n = 131, 87%), followed by gingiva (n = 9), buccal mucosa (n = 8) and lip (n = 2). The median patients' age at presentation was 34 (range: 16-40). Seven patients (5%) had Fanconi anemia with the gingiva being the most common location (4/7, 57%). All OSCCs were of keratinizing type. All cases tested for high-risk HPV (n = 34) were negative. On univariate analysis, high tumor budding was associated with decreased overall survival (OS) and distant metastasis free survival (DMFS), pattern of invasion correlated with OS and tumors with high stromal tumor infiltrating lymphocytes (sTIL) were associated with improved locoregional recurrence free survival (LRFS). Compared with patients 31 to 40-year-old, OSCC in the younger group was associated with significant less alcohol consumption (p = 0.011) and decreased DSS (p = 0.003) and DMFS (p = 0.023). On multivariate analysis, younger age (30 years or younger) was an independent prognostic factor for worse OS and DSS, whereas histologic grade was an independent prognostic factor for DSS. In summary, most OSCC in young patients occurred in non-smokers and did not occur in association with Fanconi anemia. Independent prognostic factors included age at presentation (30 years or younger) for OS and DSS, and histologic grade for DSS.

Short-Term Outcomes following Virtual Surgery-Assisted Immediate Dental Implant Placement in Free Fibula Flaps for Oncologic Mandibular Reconstruction.

BACKGROUND: Despite reports demonstrating feasibility of immediate dental implant placement in mandibular reconstruction with free fibula flaps for benign disease, this practice is not routinely used in the oncologic setting. The authors aim to demonstrate the safety of immediate dental implant placement for oncologic mandible reconstruction. METHODS: In 2017, the authors' center began immediate dental implant placement in free fibula flaps for oncologic patients undergoing mandibulectomy reconstruction. Immediate dental implant placement patients were compared to a historical cohort also reconstructed with computer-aided design and manufacturing technology beginning in 2011 (n = 34) as a noninferiority study design. Primary outcomes of interest included 90-day complications, time to radiotherapy, and time to and number of patients achieving dental restoration. RESULTS: Sixty-one patients underwent free fibula flaps following mandibulectomy using computer-aided design and manufacturing. Seventy-two dental implants were placed in the immediate dental implant placement cohort (n = 27). No differences were noted in major or minor 90-day complications between groups (p > 0.05). Radiotherapy was required in 55 percent in the immediate dental implant placement cohort versus 62 percent in the historical cohort, with no significant difference in time to radiotherapy (67.6 days versus 62.2 days, respectively). One dental implant was removed for nonosseointegration noted during vestibuloplasty. Fourteen (51.8 percent) immediate dental implant patients had complete dental restoration at 90 days compared with none in the historical cohort (p < 0.05). CONCLUSIONS: Immediate dental implant placement is a safe procedure with an unchanged short-term complication profile and no delay in radiotherapy initiation. Patients undergoing immediate dental implant placement are more likely to complete full dental rehabilitation. Long-term and health-related quality-of-life outcomes remain to be determined. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Host Factors Independently Associated With Prognosis in Patients With Oral Cavity Cancer.

Importance: The association and interaction of host characteristics with prognosis in patients with oral cavity squamous cell carcinoma (OSCC) are poorly understood. There is increasing evidence that host characteristics are associated with treatment outcomes of many cancers. Objectives: To examine the host factors associated with prognosis in patients with OSCC and their interactions to create a numerical index that quantifies the prognostic capacity of these host characteristics. Design, Setting, and Participants: This retrospective cohort study included patients with OSCC treated surgically at a tertiary care center from January 1, 1998, to December 31, 2015. From a departmental OSCC database of 1377 previously untreated patients, 68 patients with missing data on any host variable of interest within a month before the start of treatment were excluded, leaving 1309 patients. Data analysis was performed from October 21, 2019, to December 10, 2019. Exposure: Primary surgery for OSCC. Main Outcomes and Measures: Overall survival (OS) was the primary end point, and disease-specific survival (DSS) was the secondary end point. Optimal cutoffs for each variable were identified using recursive-partitioning analysis with the classification and regression tree method using OS as the dependent variable. Body mass index (BMI) and pretreatment peripheral blood leukocyte count, platelet count, hemoglobin level, and albumin level were analyzed. A host index (H-index) was developed using independent factors associated with OS. Results: A total of 1309 patients (731 [55.8%] male; mean [SD] age, 62 [14.3] years) participated in the study. When including all the host-related factors in a multivariable analysis, all except BMI (hazard ratio [HR], 1.14; 95% CI, 0.80-1.63) were independently associated with outcomes. For example, compared with a hemoglobin level of 14.1 g/dL or greater, the HR for a level of 12.9 to 14.0 g/dL was 1.42 (95% CI, 1.13-1.77) and for a level of 12.8 g/dL or less was 1.51 (95% CI, 1.18-1.94), and compared with an albumin level of 4.3 g/dL or greater, the HR for a level of 3.7 to 4.2 g/dL was 1.18 (95% CI, 0.95-1.45) and for a level of 3.6 g/dL or less was 3.64 (95% CI, 2.37-5.58). An H-index of 1.4 or less was associated with a 74% 5-year OS, an H-index of 1.5 to 3.5 with a 65% 5-year OS, and an H-index of 3.6 or higher with a 38% 5-year OS; for DSS, the 5-year survival was 84%, 80%, and 64%, respectively. Compared with patients with an H-index score of 1.4 or less, patients with H-index scores of 1.5 to 3.5 (hazard ratio, 1.474; 95% CI, 1.208-1.798) and 3.6 or higher (hazard ratio, 3.221; 95% CI, 2.557-4.058) had a higher risk of death. Conclusions and Relevance: The findings suggest that pretreatment values of neutrophils, monocytes, lymphocytes, hemoglobin, and albumin are independently associated with prognosis in patients with OSCC. The interactions between these host factors were incorporated into a novel H-index that quantified the prognostic capacity of host characteristics associated with OSCC.

Dental Implant Survival in Vascularized Bone Flaps: A Systematic Review and Meta-Analysis.

BACKGROUND: Maxillofacial reconstruction with vascularized bone restores facial contour and provides structural support and a foundation for dental rehabilitation. Routine implant placement in such cases, however, remains uncommon. This study aims to determine dental implant survival in patients undergoing vascularized maxillary or mandibular reconstruction through a systematic review of the literature. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the literature was queried for implant placement in reconstructed jaws using Medical Subject Headings terms on PubMed, Embase, and Cochrane platforms. Weighted implant survivals were calculated for the entire cohort and subcohorts stratified by radiotherapy. Meta-analyses were performed to estimate effect of radiation on implant osseointegration. RESULTS: Of 3965 publications identified, 42 were reviewed, including 1084 patients with 3636 dental implants. Weighted implant survival was 92.2 percent at a median follow-up of 36 months. Survival was 97.0 percent in 269 implants placed immediately in 60 patients versus 89.9 percent in 1897 delayed implants placed in 597 patients, with follow-up of 14 and 40 months, respectively. Dental implants without radiotherapy exposure had better survival than those exposed to radiation (95.3 versus 84.6 percent; p < 0.01) at a median follow-up of 36 months. Meta-analyses showed that radiation significantly increased the risk of implant failure (risk ratio, 4.74; p < 0.01) and suggested that implants placed before radiotherapy trended toward better survival (88.9 percent versus 83.4 percent, p = 0.07; risk ratio, 0.52; p = 0.14). CONCLUSIONS: Overall implant survival was 92.2 percent; however, radiotherapy adversely impacted outcomes. Implants placed before radiotherapy may demonstrate superior survival than implants placed after.

Long-term functional and esthetic outcomes after fibula free flap reconstruction of the mandible.

BACKGROUND: The goal of this study is to report functional and esthetic outcomes, after fibula free flap (FFF) reconstruction of the mandible for oral cancer, assessed by physicians, nonclinicians, and patients. METHODS: Twenty-five long-term survivors from oral cancer after FFF reconstruction were recalled for head and neck examination by surgeons, for photographs and patient-reported outcomes, using EORTC, QLQ-C30, H&N35, and FACE-Q questionnaires. RESULTS: Physicians reported 64% restoration of functionality compared to normal. Patients reported high scores on QLQ-C30 but lower scores on H&N35. Esthetic scores were reported higher by clinicians than nonclinicians. The decline in function and appearance was attributed to loss of lower dentition, trismus, malocclusion, xerostomia, and tissue atrophy. CONCLUSION: To minimize the decline in function and appearance, immediate dental implants in FFF, better reconstruction of the temporomandibular joint, newer methods of radiotherapy to minimize xerostomia and oral exercises to prevent trismus should be considered.

Immediate Dental Implantation in Oncologic Jaw Reconstruction: Workflow Optimization to Decrease Time to Full Dental Rehabilitation.

Full dental rehabilitation following segmental mandibulectomy or maxillectomy for oncologic tumor ablation should be the goal for every patient. But despite advances in technology and reconstructive techniques, many patients do not achieve timely or complete oral rehabilitation. Recognizing this fault, we recently adopted an innovative workflow to increase the number of patients undergoing dental restoration, irrespective of tumor pathology or need for adjuvant radiotherapy. Preoperatively, every osseous jaw reconstruction undergoes virtual surgical planning to incorporate the placement of endosseous implants into the fibula osteocutaneous free flap. The dental implants are then placed intraoperatively at the time of tumor ablation and reconstruction. Four-to-six weeks following the initial surgery, the patient returns to the operating room for vestibuloplasty and exposure of the dental implants. Within 3 days of the vestibuloplasty, a temporary dental prosthesis is placed in the dental clinic, and the patient can then begin radiation therapy if needed. Following adjuvant radiation therapy, the temporary prosthesis can be replaced with a permanent one. At our institution, this innovative workflow has allowed for earlier aesthetic restoration of the jaw and greatly expanded the number of patients able to achieve oral rehabilitation. Herein, we describe this innovative workflow and provide technical pearls for successful execution.

A Virtual Surgical Planning Algorithm for Delayed Maxillomandibular Reconstruction.

BACKGROUND: The absence of a tumor specimen from which to obtain measurements at the time of delayed maxillomandibular reconstruction introduces degrees of uncertainty, creating the need for substantial intraoperative guesswork by the surgeon. Using the virtual surgical planning environment, the size and shape of missing bony elements is determined, effectively "recreating the defect" in advance of the surgery. Three virtual surgical planning techniques assist the reconstructive surgeon: patient-specific modeling, mirroring the normal contralateral side, and scaled normative data. To facilitate delayed reconstruction a hierarchical algorithm using virtual surgical planning techniques was developed. METHODS: Delayed maxillomandibular virtual surgical planning reconstructions were identified from 2009 to 2016. Demographics, modeling techniques, and surgical characteristics were analyzed. RESULTS: Sixteen reconstructions were performed for osteoradionecrosis with displacement (50.0 percent) or oncologic defects (37.5 percent). Most patients had prior surgery (81.3 percent) and preoperative radiation therapy (81.3 percent); four had failed prior reconstructions. The following delayed virtual surgical planning techniques were used: patient-specific modeling based on previous imaging (43.8 percent), mirroring normal contralateral anatomy (37.5 percent), and scaled normative data (18.8 percent). Normative and mirrored reconstructions were designed to restore normal anatomy; however, most patient-specific virtual surgical planning designs (71.4 percent) required nonanatomical reconstructions to accommodate soft-tissue limitations and to avoid the need for a second flap. One partial flap loss required a second free flap, and one total flap failure occurred. Hardware exposure was the most common minor complication, followed by infection, dehiscence, and sinus tract formation. CONCLUSIONS: Virtual surgical planning has inherent advantages in delayed reconstruction when compared to traditional flap shaping techniques. An algorithmic approach based on available imaging and remaining native anatomy enables accurate reconstructive planning followed by flap transfer without the need for intraoperative guesswork. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Ameloblastomas of the mandible and maxilla.

Ameloblastoma is a histologically benign but locally aggressive tumor of the jaws. We conducted a retrospective cohort study to review the clinical, radiologic, and pathologic features of patients with ameloblastoma of the mandible and maxilla and to report the outcomes of treatment. Our study population was made up of a series of 30 consecutively presenting patients-15 men and 15 women, aged 19 to 81 years (median: 61.5)-who had undergone their primary treatment of ameloblastoma of the mandible or maxilla at Memorial Sloan Kettering Cancer Center from January 1987 through December 2012. In addition to demographic data, we compiled information on clinical characteristics, imaging findings, the type of surgery, surgical margins, adjuvant treatments, histologic patterns, length of follow-up, time to recurrence, treatment of recurrence, and factors that had an influence on recurrence. All but 2 patients with negative margins were cured. Favorable outcomes were associated with the administration of adjuvant postoperative radiotherapy for patients with positive margins and a repeat resection for patients with recurrences. Complete excision with negative margins, however, remains the gold standard for curative treatment.

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.

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.

Impact of elective neck dissection on the outcome of oral squamous cell carcinomas arising in the maxillary alveolus and hard palate.

BACKGROUND: Whether elective lymph neck dissection (ELND) is associated with improved survival in oral squamous cell carcinomas (SCC) of the maxillary alveolus/hard palate is not known. METHODS: One hundred ninety-nine patients presenting de novo and receiving treatment for clinically node negative SCC of the maxillary alveolus/hard palate at 2 cancer centers between 1985 and 2011 were analyzed. RESULTS: Forty-two patients (21%) received ELND. Occult nodal metastases were present in 29% of the dissected necks. The ELND group had more T3 to T4 status tumors (62% vs 34%; p < .001) and positive-margin resections (59% vs 38%; p = .019). Patients undergoing ELND experienced lower rates of neck recurrence (6% vs 21%; p = .031), superior 5-year recurrence-free survival (68% vs 45%; p = .026), and overall survival (86% vs 62%; p = .043). ELND was associated with a 2-fold decrease in risk of recurrence in multivariable analysis. CONCLUSION: ELND was associated with lower rates of recurrence and improved survival in SCC of the maxillary alveolus/hard palate. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1688-E1694, 2016.

Irradiation for locoregionally recurrent, never-irradiated oral cavity cancers.

BACKGROUND: The purpose of this study was to report the clinical outcomes and related prognostic factors of patients who underwent radiotherapy (RT) for the treatment of recurrent, never-irradiated oral cavity cancer (recurrent OCC). METHODS: The records of consecutive patients with nonmetastatic recurrent OCC who presented to and were treated with RT at our institution between 1989 and 2011 were reviewed. The Kaplan-Meier method was used to calculate overall survival (OS). The cumulative incidences of disease-specific death, local failure, regional failure, and distant metastasis were calculated with death as a competing risk. RESULTS: One hundred twenty-three patients were identified. Median follow-up for living patients was 54 months and 16 months for all patients. Ninety-one patients had salvage surgery followed by adjuvant RT. Definitive RT was utilized in the remaining 32 patients. The 5-year OS was 40%. The 5-year cumulative incidence of disease-specific death, local failure, regional failure, and distant metastasis was 55%, 34%, 22%, and 20%, respectively. Recurrent T classification and lack of salvage surgery were independently associated with worse disease-specific death and decreased OS, respectively. Subset analysis of patients who underwent salvage surgery demonstrated that age, recurrent T classification, and perineural invasion (PNI) were independently associated with decreased OS; recurrent T classification and thicker tumors were independently associated with worse disease-specific death; and positive/close margins and primary T classification were independently associated with increased local failure. CONCLUSION: In this group of patients with recurrent OCC, clinical outcomes were similar or improved when compared with other recurrent OCC-specific reports. In the salvage surgery subset, tumor thickness and PNI are recurrent pathologic features associated with outcomes that were only previously demonstrated in studies of primary disease. Because of the relatively worse outcomes in patients receiving definitive or adjuvant RT for recurrent OCC, we advocate for the appropriate use of postoperative RT in the initial management of oral cavity cancers.

A novel tumor: specimen index for assessing adequacy of resection in early stage oral tongue cancer.

PURPOSE: Surgical margin status frequently affects decisions regarding adjuvant treatment; however, reporting and interpretation of surgical margins is subject to considerable subjectivity because of many factors including the adequacy of resection. We developed a novel measure of the adequacy of surgical resection, the tumor: specimen index (TSI), and tested its utility at predicting clinical outcomes in a retrospective cohort study. PATIENTS AND METHODS: An institutional database was queried to identify previously untreated patients with T1 and T2 oral tongue cancer who underwent surgery during 1985-2009 (n=433). The TSI, a geometric mean representing the percentage of the surgical specimen that is occupied by the tumor in average single dimension, was calculated from the largest measured lengths, widths, and heights of the tumor in relation to the entire surgical specimen. Multivariate analyses of locoregional recurrence-free probability (LRRFP) and disease-specific survival (DSS) were performed with commonly accepted prognosticators in addition to TSI and surgical margins status. RESULTS: The mean TSI was 41 (range 11-90; SD 14). Surgical margin status was associated with TSI; margins were negative in 84% of patients with TSI<45 and in 63% of patients with TSI⩾45 (p<0.001). TSI⩾45 was associated with worse LRRFP (57% vs. 76%, p<0.001) and worse DSS (68% vs. 85%, p<0.001). In a multivariate analysis that did not include TSI, surgical margin status independently predicted LRRFP (p=0.014) but not DSS. When TSI was included, only TSI, and not surgical margin status, was an independent predictor of both LRRFP (p=0.002) and DSS (p=0.011). CONCLUSION: The tumor: specimen index is an easily-calculated metric for estimating the adequacy of 3-dimensional resection in T1 and T2 oral tongue cancer that independently predicts oncologic outcomes.

Pathologically determined tumor volume vs pathologic T stage in the prediction of outcome after surgical treatment of oropharyngeal squamous cell carcinoma.

IMPORTANCE: Traditional prognostic models for squamous cell carcinoma of the head and neck are based on the TNM staging system. However, there is growing evidence that tumor volume (TV) may be a more accurate predictor of outcome. OBJECTIVE: To determine whether pathologic TV (pTV) in patients with oropharyngeal squamous cell carcinoma treated surgically is a more significant predictor of outcome compared with pathologic tumor (pT) stage. DESIGN, SETTING, AND PARTICIPANTS: Review of patients whose treatment was managed between January 1, 1985, and December 2005 at a US tertiary referral cancer center. The participants included 159 patients who had undergone primary surgery for oropharyngeal squamous cell carcinoma and had 3 dimensions reported on histopathologic testing. MAIN OUTCOMES AND MEASURES: The pTV was calculated as the product of the 3 dimensions expressed in cubic centimeters. For comparison of pT stage with pTV in outcome prediction, concordance indexes were generated using the bootstrap method (n = 1000) to quantify the predictive accuracy of recurrence and survival outcomes. Concordance indexes were then compared and a significant difference was considered when P < .05. RESULTS: The median age of the patients was 59 years (range, 22-84 years) and 106 were male (67%). Sites of the tumors were base of the tongue (86 patients [54%]), tonsil (48 [30%]), soft palate (24 [15%]), and posterior pharyngeal wall (1 [1%]). The median follow-up time was 64 months (range, 1-272 months). The median tumor volume was 6.8 cm3 (range, 0.1-162.5 cm³). Pathologic TV was a significant predictor of disease-specific mortality. Unlike pT stage, pTV was a significant predictor of local recurrence, regional recurrence, and distant recurrence. Comparison of concordance indexes showed that pTV was a significantly better predictor of disease-specific mortality, local recurrence, and distant recurrence (all P < .05). CONCLUSIONS AND RELEVANCE: Pathologic TV outperforms pT stage in the prediction of outcome following surgical treatment of oropharyngeal cancer. Tumor volume should be considered in the design of prospective surgical trials.

High rates of regional failure in squamous cell carcinoma of the hard palate and maxillary alveolus.

BACKGROUND: The purpose of this study was to determine the incidence of neck metastasis in hard palate and maxillary alveolus squamous cell carcinoma (SCC) and to identify factors predictive of regional failure. METHODS: In 139 patients treated for SCC of the hard palate and maxillary alveolus (from 1985-2006), the incidence rates of regional metastasis at presentation and at recurrence were calculated. Factors predictive of regional recurrence-free survival were identified on Cox multivariable regression analysis. RESULTS: Regional failure occurred in 28.4% of patients and was significantly associated with pathologic T classification, ranging from 18.7% (pT1) to 37.3% (pT4). T classification was an independent predictor of regional recurrence-free survival (RRFS) on multivariable analysis. Most patients (65.6%) with regional recurrence were not able to be salvaged. CONCLUSION: Patients with T2 to T4 primary tumors of the hard palate and maxillary alveolus exhibited high rates of regional failure. In most cases, successful salvage was not achieved. Elective treatment of the neck with surgery or radiation is therefore recommended.