A comparative study between submandibular-facial artery island flaps (including perforator flap) and submental artery perforator flap: A novel flap in oral cavity reconstruction Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): Xin-rong Ou, Tong Su, Long Huang, Can-hua Jiang, Feng Guo, Ning Li, An-jie Min, Xin-chun Jian Abstract Objective The purpose of this study was to introduce submandibular-facial artery island flaps (S-FAIF), including the perforator flap, and to evaluate their application for intraoral reconstruction in comparison with submental artery perforator flaps (SMAPF). Methods Ninety-six patients who underwent intraoral reconstruction using an S-FAIF (n = 34) or SMAPF (n = 62) after cancer resection were recruited in this study. The flap characteristics (viz., pedicle length, flap size, venous drainage pattern, and harvest time), short-term outcomes (viz., flap partial loss, intraoral wound dehiscence, fistula, and wound infection), and long-term morbidity (viz., facial nerve palsy, neck motion restriction, and hair growth) were compared. Results Nine S-FAIFs were authentic perforator flaps pedicled by level Ⅰ facial artery perforators, while the rest were island flaps based on level Ⅱ facial artery perforators. The survival rates of S-FAIF and SMAPF were both 100 percent. Flap partial loss occurred in two patients in each group. The pedicle length of S-FAIF was shorter than that of SMAPF (p < 0.001). Statistics analysis revealed no significant difference regarding flap size, venous drainage pattern, short-term outcomes, neck motion restriction, or facial nerve palsy between the groups. S-FAIF required less harvest time (p < 0.001) and experienced less hair growth when compared to SMAPF (p = 0.011). Conclusions The S-FAIF is a robust and reliable novel flap and on par with SMAPF for reconstruction of small and medium-sized intraoral defects. It is preferred to SMAPF when technical requirements for flap harvest and hair problems are considered. It should be supplemented to the armamentarium for intraoral reconstruction.

Use of a non-ICU specialty ward for immediate post-operative management of head and neck free flaps; a randomized controlled trial Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): B. Cervenka, L. Olinde, E. Gould, D.G. Farwell, M. Moore, M. Kaufman, A.F. Bewley Abstract Objectives Compare length of stay, flap failure rate, medical and surgical complications and cost when patients undergoing head and neck free flap reconstruction are monitored in an intensive care unit (ICU) versus a specialty ward unit postoperatively. Materials and methods A prospective, non-inferiority, randomized controlled trial was conducted from 7/22/2016 to 9/12/2018 at a single institution. Patients were randomized to the ICU or specialty ward unit. Flap check protocols were identical between the groups. Perioperative and postoperative outcome variables were assessed and compared. Results 131 patients were enrolled in the study and 118 ultimately underwent head and neck free flap reconstruction. 57 were randomized to the ICU and 61 to the specialty ward unit. There were no significant differences between the ICU and specialty ward unit groups with regard to demographic variables including age, gender, co-morbidities, tobacco or alcohol use, prior chemotherapy or radiation therapy treatment. There were no significant differences in perioperative variables including need for transfusion, tracheostomy, ischemia time, blood loss, fluid administration or post-operative antibiotic use. There was no significant difference in the primary outcome variable, length of stay. There were no significant differences in the number of the medical or surgical complications, flap failure rate, or hospital costs. Conclusion In this prospective, randomized controlled trial, head and neck free-flap patients cared for on a specialty ward in the immediate post-operative period had equivalent outcomes to those cared for in the ICU.

Development and validation of a nomogram incorporating selected systemic inflammation-based prognostic marker for complication prediction after vascularized fibula flap reconstruction Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): Zhongqi Liu, Haixuan Wu, Ning Liufu, Shi Cheng, Haoquan Huang, Chuwen Hu, Minghui Cao Abstract Objective To develop and validate a nomogram incorporating systemic inflammatory markers (the Albumin/NLR Score [ANS]) to predict postoperative complications after vascularized fibula flap reconstruction. Patients and methods A total of 238 patients who underwent vascularized fibula flap reconstruction between March 2012 and December 2016 were collected as the primary cohort. Univariable and multivariable analysis were performed to identify independent risk factors for postoperative complications. Backward stepwise logistic regression analysis was then applied with and without the ANS; and nomograms were established based on these criteria. Independent validation of these nomograms was carried out in an independent validation cohort including 106 consecutive patients from December 2016 and January 2018. Results Radiotherapy history (odds ratio [OR] = 0.336; 95% CI, 0.157–0.717; P = 0.005), the ANS (OR = 0.248; 95% CI, 0.093–0.661; P = 0.005) and fluid infusion rate over 24 h (OR = 0.671; 95% CI, 0.479–0.94; P = 0.02) were identified as independent risk factors for postoperative complications. A higher C-index was found in both the primary (0.759; 95% CI, 0.719–0.739) and validation cohort (0.704; 95% CI, 0.613–0.659) for the nomogram incorporating the ANS, and NRI was 0.496 (95% CI, 0.072–0.920; P = 0.022) comparing of these nomograms. Furthermore, a wider threshold probability (0.2–0.9) and superior clinical value were observed in the nomogram incorporating the ANS on the decision curve. Conclusion The ANS was an independent risk factor for postoperative complications associated with vascularized fibula flap reconstruction. The nomogram incorporating the ANS was established with better accuracy and showed more potential clinical benefit for the estimation of postoperative complications.

Management of retropharyngeal lymph node metastasis in oral cancer Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): Yu Oikawa, Yasuyuki Michi, Fumihiko Tsushima, Hirofumi Tomioka, Yumi Mochizuki, Takuma Kugimoto, Toshimitsu Osako, Hitomi Nojima, Misaki Yokokawa, Yoshihisa Kashima, Hiroyuki Harada Abstract Objectives Retropharyngeal lymph node (RPLN) metastasis is extremely rare, and prognosis is significantly poor in oral cancer. We retrospectively examined the management of RPLN metastases in oral cancer. Materials and methods A total of 1247 patients with oral cancer were treated at our department from January 2002 and December 2016. Among these patients, 374 (30%) had histologically positive lymph node metastases. Of these, 15 patients (1.2%) were diagnosed with RPLN metastases. We evaluated the diagnostic period, size, recurrence pattern, laterality, treatment, and therapeutic outcomes. The Kaplan–Meier method was used to determine overall survival (OS) among the RPLN metastasis group, cervical lymph node (CLN) metastases group, and treatment methods group for RPLN metastases. Results One patient had RPLN involvement at the initial treatment, and RPLN involvement in other patients was found subsequently. The mean duration in confirming RPLN metastases was 228 days (range, 50–867 days). Surgical therapy was performed in 5 patients, chemoradiotherapy in 7 patients, and best supported care (BSC) in 3 patients. The cumulative 5-year OS rate for the RPLN metastasis group (n = 15) was 38.1%, compared with the rate of 71.3% for the CLN group (n = 359). Regarding the therapeutic approach for RPLN metastases, OS rates were 80.0% (n = 5) in the surgical therapy group, 28.6% (n = 7) in the chemoradiotherapy group, and 0% (n = 3) in the BSC group. Conclusion Early detection and surgical treatment of RPLN metastases are associated with increased survival rate in oral cancer.

Advanced adenoid cystic carcinoma of the skull base – The role of surgery Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): Emily Guazzo, James Bowman, Sandro Porceddu, Lachlan Webb, Benedict Panizza Abstract Background Adenoid cystic carcinoma (ACC) is a salivary gland malignancy with a propensity for perineural spread and diffuse soft tissue infiltration. In the head and neck this unique biological behaviour can result in skull base involvement. A lack of consensus regarding management of ACC involving the skull base in conjunction with the technical and reconstructive challenges of oncological resection in this region has led to variation in practice between institutions. Method Retrospective multicentre review of patients with advanced ACC infiltrating the skull base, treated surgically by the Queensland Skull Base Unit between 2005 and 2017, with a minimum follow up time of 24  months. Results 32 patients were treated for ACC with skull base involvement with oncological resection and post-operative radiation in the study period with a median follow up of 82.18  months (33.11–159.53 months). 5 and 10  year locoregional control were both 88.2% (95% CI 67.5–96.1) despite a high rate of microscopically positive margins (81.3%). Metastatic disease rates were high, resulting in low rates of disease free survival (DFS) (53.0% at 5 years (95% CI 33.7–69.0) and 23.0% at 10 years (9.5–39.8)). Overall survival (OS) was high (5 year 91.8% (95% CI 71.1–97.9), 10 year 63.7% (95% 37.5–81.2)), despite the advanced nature of disease. Conclusion High rates of locoregional control can be achieved in skull base ACC with oncological resection of disease and post-operative radiation. Whilst disease recurrence rates are high, a majority of recurrence is metastatic and does not confer poor intermediate term overall survival.

Alterations in composition of immune cells and impairment of anti-tumor immune response in aged oral cancer-bearing mice Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): Katsuhisa Sekido, Kei Tomihara, Hidetake Tachinami, Wataru Heshiki, Kotaro Sakurai, Rohan Moniruzzaman, Shuichi Imaue, Kumiko Fujiwara, Makoto Noguchi Abstract Objectives Aging has been suggested to be associated with immune dysregulation. An understanding of alterations in the host immunity with advancing age is, therefore, important for designing immune therapy for elderly cancer patients. In this context, not much is known about age-associated alterations in the immune system in oral cancer. Methods To evaluate age-associated alterations in the immune system, which might affect anti-tumor immune responses in oral cancer, we performed a comparative analysis of the proportion of different immune cells, the proliferative capacity of T cell compartment, and the response against immune therapies targeting immune check point molecules between young and aged oral cancer-bearing mice. Results The proportion of immune regulatory cells, such as regulatory T cells and myeloid derived suppressor cells, was significantly increased in aged mice compared to that in young mice. Moreover, the expression of PD-1 and CTLA-4 on both CD4+ and CD8+ T cells was elevated in aged mice compared to that in young mice, and the proliferative abilities of CD4+ and CD8+ T cells derived from aged mice were significantly reduced following stimulation of T-cell receptors. Moreover, tumor growth was significantly enhanced in aged mice compared to that in young mice. However, immunotherapies targeting PD-1, CTLA-4, and PD-L1 resulted in faster tumor regression in aged mice than in young mice. Conclusions Together, our results indicate that age-associated alterations in the immune system are directly associated with the impairment of anti-tumor immunity in aged mice bearing oral cancer, and might facilitate the progression of the tumor.

Reconstruction of maxillectomy and midfacial defects using latissimus dorsi-scapular free flaps in a comprehensive cancer center Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): A. Moya-Plana, M. Veyrat, J.F. Honart, K. de Fremicourt, H. Alkhashnam, B. Sarfati, F. Janot, N. Leymarie, S. Temam, F. Kolb Abstract Background The standard of care for sinonasal malignancies is a large surgical resection followed by radiotherapy. Midfacial defects resulting from maxillectomy require a complex reconstruction procedure. Given their adaptability, chimeric flaps such as latissimus dorsi-scapular (LDS) free flaps appear to be a good option. Material & methods We performed a single-center retrospective study of consecutive patients with sinonasal cancers where a LDS free flap was used for reconstruction. We assessed the postoperative complications and the functional, aesthetic and oncologic outcomes. Results Eighty-four patients were included. Primary tumors were staged as T4a in 68% of cases; 38.3% of the patients received induction chemotherapy and 82.7% received adjuvant radiotherapy. Based on our classification of midfacial and palatal defects, the majority of the patients (69%) had a type IIa with interruption of the three facial pillars. The orbital floor was removed in 55.9% of cases. The median follow-up was 45 months. Total flap necrosis with no possible revascularization occurred in 5.9% of cases. For the orbital reconstruction, a revision procedure was needed for necrosis and/or infection of the costal cartilage graft in eight cases (17%). More than 90% of the patients had no functional disorders regarding speaking, swallowing and chewing. Soft palate involvement was a prognostic factor of speech (p < 10−4) and swallowing (p = .005) disorders. Dental rehabilitation was realized in 70.2% of the patients. No severe complications were observed in the donor site, except for one seroma. Conclusion A LDS free flap is a reliable technique for the reconstruction of complex midfacial defects.

Addition of S-1 to radiotherapy for treatment of T2N0 glottic cancer: Results of the multiple-center retrospective cohort study in Japan with a propensity score analysis Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): Daisuke Sano, Teruhiko Tanabe, Akira Kubota, Shunsuke Miyamoto, Yuji Tanigaki, Kenji Okami, Masanori Komatsu, Ryo Ikoma, Kazumasa Suzuki, Yoshihiro Akazawa, Sei Kobayashi, Yoshihiro Yamada, Nobuhiko Oridate Abstract Objectives This multicenter retrospective cohort study aimed to evaluate the significance of adding S-1 to radiotherapy (RT) for the treatment of T2N0 glottic cancer using a propensity score matched analysis in Japan. Materials and Methods This study was conducted on 287 patients with T2N0 glottic cancer who were treated with definitive RT or chemoradiotherapy with S-1 (S-1 RT) between April 2007 and March 2017. Propensity score matched analysis was performed to ensure the well-balanced characteristics of the groups of patients who received RT alone and S-1 RT. Overall, progression-free and laryngectomy-free survivals and local control and laryngeal preservation rates were compared. Results Fifty-four pairs of patients were selected after performing propensity score matched analysis. Clinical characteristics were well-balanced between the two groups. The overall survival of patients in the S-1 RT group was significantly better than those in the RT alone group (P = 0.008). The progression-free and laryngectomy-free survivals of patients in the S-1 RT group were also better than those in the RT alone group; however, the differences were not significant. In contrast, patients in the S-1 RT group had slightly lower local control and laryngeal preservation rates compared with those in the RT alone group. The incidence of dermatitis in the S-1 RT group was significantly higher than that in the RT alone group in the matched population (P = 0.013). Conclusions The addition of S-1 to RT for the treatment of T2N0 glottic cancer was not associated with better local control and laryngeal preservation rates in this study.

Navigation-guided osteotomies improve margin delineation in tumors involving the sinonasal area: A preclinical study Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): Marco Ferrari, Michael J. Daly, Catriona M. Douglas, Harley H.L. Chan, Jimmy Qiu, Alberto Deganello, Stefano Taboni, Carissa M. Thomas, Axel Sahovaler, Ashok R. Jethwa, Wael Hasan, Piero Nicolai, Ralph W. Gilbert, Jonathan C. Irish Abstract Objectives To demonstrate and quantify, in a preclinical setting, the benefit of three-dimensional (3D) navigation guidance for margin delineation during ablative open surgery for advanced sinonasal cancer. Materials and methods Seven tumor models were created. 3D images were acquired with cone beam computed tomography, and 3D tumor segmentations were contoured. Eight surgeons with variable experience were recruited for the simulation of osteotomies. Three simulations were performed: 1) Unguided, 2) Guided using real-time tool tracking with 3D tumor segmentation (tumor-guided), and 3) Guided by 3D visualization of both the tumor and 1-cm margin segmentations (margin-guided). Analysis of cutting planes was performed and distance from the tumor surface was classified as follows: “intratumoral” when 0 mm or negative, “close” when greater than 0 mm and less than or equal to 5 mm, “adequate” when greater than 5 mm and less than or equal to 15 mm, and “excessive” over 15 mm. The three techniques (unguided, tumor-guided, margin-guided) were statistically compared. Results The use of 3D navigation for margin delineation significantly improved control of margins: unguided cuts had 18.1% intratumoral cuts compared to 0% intratumoral cuts with 3D navigation (p < 0.0001). Conclusion This preclinical study has demonstrated the significant benefit of navigation-guided osteotomies for sinonasal tumors. Translation into the clinical setting – with rigorous assessment of oncological outcomes – would be the proposed next step.

Prognostic value of radiologic extranodal extension and its potential role in future N classification for nasopharyngeal carcinoma Publication date: December 2019 Source: Oral Oncology, Volume 99 Author(s): Tianzhu Lu, Yujun Hu, Youping Xiao, Qiaojuan Guo, Shao Hui Huang, Brian O'Sullivan, Yanhong Fang, Jingfeng Zong, Ying Chen, Shaojun Lin, Yunbin Chen, Jianji Pan Abstract Purpose We evaluated the prognostic value of various grades of radiologic extranodal extension (rENE) and their potential roles in N-classification refinement for nasopharyngeal carcinoma (NPC). Methods and Materials All NPC patients treated with IMRT in our institution between 2005 and 2011 were included. Pre-treatment MR of cN+ cases were reviewed and rENE was recorded asG0: lymph nodes (LNs) without rENE; G1: tumor infiltrating beyond individual nodal capsule(s) into the surrounding fat plane; G2: coalescent nodal mass with unequivocal evidence of rENE; G3: tumor infiltrating beyond nodal capsule into adjacent structures. Multivariable analysis (MVA) assessed prognostic value of rENE for distant metastasis (DM) and death adjusted for age, gender, LDH, T-classification, N-classification, and chemotherapy cycles. Results A total of 1390 of 1616 (86%) NPC were cN+, and rENE was detected in 826/1390 (59%) patients: 256 (18.4%) G1-rENE, 487 (35%) G2-rENE, and 83 (6%) G3-rENE. MVA confirmed that G2-/G3-rENE had increased risk of DM (HR: 2.05/3.18, both p < 0.001) and death (HR: 1.62/2.39, p = 0.002/p < 0.001), while G1-rENE was non-prognostic (DM: p = 0.172; death: p = 0.320). We propose a refined N: New-N1: N1/N2 without G2-/G3-rENE; New-N2: N1_G2-rENE; New-N3: N2_G2-rENE, N1/N2_G3-rENE, or N3. The New-N classification had a lower AIC and higher c-index for DM (AIC: 3809.6 vs 3830.9; c-index: 0.700 vs. 0.677) and death (AIC: 3693.8 vs. 3705.9; c-index: 0.735 vs. 0.725) versus TNM-8 N. Conclusions G2- and G3-rENE are independently prognostic for DM and death in NPC. Compared to the TNM8 N-classification, a refined N-classification incorporating G2- and G3-rENE improves prognostication of DM and mortality risk.