Prognostic significance of adjuvant therapy and specific radiation dosages in Taiwanese patients with oral cavity cancer and extra-nodal extension: a nationwide cohort study.

BACKGROUND: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. METHODS: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. RESULTS: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 - 7000 cGy, n = 1155 versus 6000 - 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578). CONCLUSIONS: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600-7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients.

Prophylactic Versus Reactive Megestrol Acetate Use for Critical Body Weight Loss in Patients with Pharyngeal and Laryngeal Squamous Cell Carcinoma Undergoing Concurrent Chemoradiotherapy.

This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC).Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared.The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p = .001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p = .011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p < .001). Less neutropenia (26.0% vs. 70.0% [p < .001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p = .009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort.p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC.

Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study.

BACKGROUND: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. METHODS: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. RESULTS: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81]). CONCLUSION: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification.

A Comparison Study of Outcomes and Complications Between Marginal Mandibulectomy With or Without Additional Mandibulotomy in Tongue Cancers.

BACKGROUND: Marginal mandibulectomy with or without additional mandibulotomy could represent the alternatives to avoid segmental mandibulectomy in carefully selected tongue cancers. AIM AND OBJECTIVES: This study investigated a subgroup of tongue cancers with suspected involvement to the alveolar bone because of the shallow and deformed mouth floor. We aimed to compare the functional outcomes, postoperative complications, and disease control efficacy between the 2 different marginal mandibulectomy approaches, with or without additional mandibulotomy. MATERIALS AND METHODS: A retrospective study of 29 marginal mandibulectomies and 26 combined mandibulotomies for tongue cancer wide excisions and flap reconstruction at Chang Gung Memorial Hospital Linkou Branch during 2014 to 2019 was performed. RESULTS: The combined mandibulotomy group had more advanced T-status ( P < 0.001) and greater tumor diameters ( P < 0.001) but not increased preexisting trismus, bone invasions, or positive margins. The additional mandibulotomy increased flap necrosis ( P = 0.044), late infections ( P = 0.004), and tongue movement limitations ( P = 0.044) but not osteoradionecrosis. Osteoradionecrosis was unrelated to the resected mandibular length or the mandibulotomy sites. Feeding tube dependence was greater in the combined group at discharge ( P = 0.014), but no long-term differences were noted. Kaplan-Meier overall survival ( P = 0.052) and disease-free survival ( P = 0.670) were both comparable between the 2 groups. CONCLUSIONS: The combined procedure of mandibulotomy and marginal mandibulectomy in large tongue cancers without bone invasions is associated with increased soft tissue-related complications but not bone-related complications. However, comparable disease control, survival, and long-term tube feeding outcomes were noted.

Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Factors impacting posttraumatic growth in head-and-neck cancer patients with oncologic emergencies.

PURPOSE: To identify factors associated with posttraumatic growth (PTG) of head-and-neck cancer squamous cancer (HNC) patients with oncologic emergencies (OE) within the first six months post-treatment. METHODS: We conducted a cross-sectional study of HNC patients in Taiwan from May 2019 to April 2021 using patient-reported outcomes. Patients were assessed for symptom distress, anxiety, fear of recurrence (FCR), and PTG. Multiple regression analysis was conducted to identify factors associated with PTG. The independent-samples t-test was used to compare PTG and its five specific domains in patients with low FCR, high FCR, low anxiety, and high anxiety. RESULTS: Of the 114 patients surveyed, 46.5% reported little-to-no PTG, and 53.5% had moderate-to-high PTG. Greater PTG was associated with greater FCR, longer time since OE, less anxiety, having a cancer recurrence, and greater educational attainment. These factors explained 38.6% of the variance in PTG. CONCLUSION: A notable proportion of HNC patients with OE-reported PTG but almost half-reported little-to-no PTG. PTG occurred most in the domain of appreciation of life. The study results also suggest that training patients in coping skills and inviting them to group growth experiences can help them increase PTG and cope with cancer-related psychological threats related to OE.

Venous Size Discrepancy Is a Critical Factor When Using Superficial Temporal Vessels as Recipient Vessels for Free Flaps.

BACKGROUND: Superficial temporal vessels have been used successfully as recipient vessels for head and neck reconstruction. This study evaluates the impact of several treatment variables on flap failure and take-back rate when using these recipient vessels. METHODS: We conducted a retrospective study of all microsurgical reconstructions using superficial temporal vessels as recipient vessels in a period of 10 years. Variables collected included previous treatments (radiotherapy, chemotherapy, neck dissection, free flap reconstruction), type of flaps used (soft tissue, osteocutaneous), and vessel size discrepancy between donor and recipient vessels. RESULTS: A total of 132 patients were included in the study. The flap success rate was 98.5%. The take-back rate was 10.6%. The most frequent reason for take-back was venous congestion secondary to thrombosis. None of the studied variables was associated with flap failure. Reconstructions using osteocutaneous flaps and vein diameter discrepancy (ratio ≥ 2:1) had significantly higher take-back rates. CONCLUSION: Flaps with a significant size discrepancy between donor and recipient veins (ratio ≥ 2:1) and fibula flaps (compared with soft tissue flaps) were associated with a higher risk of take-back. It is crucial to minimize venous engorgement during flap harvest and anastomosis, and limit vein redundancy during flap in-setting.

Association between multidisciplinary team care and the completion of treatment for oral squamous cell carcinoma: A cohort population-based study.

OBJECTIVES: This study investigates the relationship between multidisciplinary team care (MDTC) and patient completion of their treatment regimen for oral squamous cell carcinoma (OSCC). METHODS: We conducted a retrospective cohort study in patients diagnosed with OSCC in Taiwan from 1 January 2016 to 30 June 2018 using a linked cancer registry database. RESULTS: Of the 969 OSCC MDTC patients in the study cohort, 6.3% reported incomplete treatment, with 1.3% interrupting ongoing treatment and 5.0% terminating definitive treatment. Patients who had advanced-stage disease, experienced primary cancer recurrence or a secondary cancer, or were treated with surgery combined with chemotherapy, radiotherapy or chemoradiotherapy were more likely to terminate treatment before completion. The major reasons for interruption of ongoing treatment included 'patient or their family considered the patient to be in poor physical condition' and 'difficulty enduring physical discomfort caused by treatment'. The major reason for termination of definitive treatment was 'patient or their families or friends experienced negative treatment effects and worried about the side-effects of treatment'. CONCLUSION: Advanced-stage cancer, recurrence or secondary cancer, and surgery combined with chemotherapy, radiotherapy or chemoradiotherapy negatively affected treatment completion. MDTC allows for shared decision-making to determine the optimal treatment.

Comparison of 18F-FDG PET/MRI, MRI, and 18F-FDG PET/CT for the detection of synchronous cancers and distant metastases in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma.

PURPOSE: In this prospective study, we sought to compare the clinical utility of fluorodeoxyglucose PET/MRI, MRI, and PET/CT in the detection of synchronous cancers and distant metastases in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC). METHODS: We examined 198 consecutive patients with biopsy-proven OHSCC who agreed to receive chemoradiation. All patients underwent pretreatment PET/MRI and PET/CT on the same day. Patients were followed-up for a minimum of 12 months or until death. The McNemar's test and receiver-operating characteristic (ROC) curves were used to compare sensitivity/specificity and the diagnostic capabilities of PET/MRI, MRI, and PET/CT, respectively. RESULTS: We identified 55 patients (27.7%) who had synchronous cancers and/or distant metastases (number of involved sites: 83). The results of site-based analysis revealed that the sensitivity of PET/MRI was 15.7% higher than that of MRI (73.5% versus 57.8%, p < 0.001) and 3.6% higher compared with PET/CT (73.5% versus 69.9%, p = 0.083), whereas the sensitivity of PET/CT was 12.1% higher than that of MRI (69.9% versus 57.8%, p = 0.012). On a patient-basis, ROC curve analysis demonstrated that PET/MRI yielded a greater area under curve than MRI (0.930 versus 0.905, p = 0.023). There were no significant differences in terms of diagnostic capability between MRI and PET/CT (0.905 versus 0.917, p = 0.469) and between PET/MRI and PET/CT (0.930 versus 0.917, p = 0.062). CONCLUSIONS: In our cohort, PET/MRI showed a significantly higher diagnostic capability than MRI and no significant difference compared with PET/CT for the detection of synchronous cancers or distant metastases in patients with OHSCC.

A combined analysis of maximum standardized uptake value on FDG-PET, genetic markers, and clinicopathological risk factors in the prognostic stratification of patients with resected oral cavity squamous cell carcinoma.

OBJECTIVE: Clinical outcomes of patients with resected oral cavity squamous cell carcinoma (OCSCC) chiefly depend on the presence of specific clinicopathological risk factors (RFs). Here, we performed a combined analysis of FDG-PET, genetic markers, and clinicopathological RFs in an effort to improve prognostic stratification. METHODS: We retrospectively reviewed the clinical records of 2036 consecutive patients with first primary OCSCC who underwent surgery between 1996 and 2016. Of them, 345 underwent ultra-deep targeted sequencing (UDTS, between 1996 and 2011) and 168 whole exome sequencing (WES, between 2007 and 2016). Preoperative FDG-PET imaging was performed in 1135 patients from 2001 to 2016. Complete data on FDG-PET, genetic markers, and clinicopathological RFs were available for 327 patients. RESULTS: Using log-ranked tests based on 5-year disease-free survival (DFS), the optimal cutoff points for maximum standardized uptake values (SUV-max) of the primary tumor and neck metastatic nodes were 22.8 and 9.7, respectively. The 5-year DFS rates were as follows: SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7 (n = 77) versus SUVtumor-max < 22.8 and SUVnodal-max < 9.7 (n = 250), 32%/62%, P < 0.001; positive UDTS or WES gene panel (n = 64) versus negative (n = 263), 25%/62%, P < 0.001; pN3b (n = 165) versus pN1-2 (n = 162), 42%/68%, P < 0.001. On multivariate analyses, SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7, a positive UDTS/WES gene panel, and pN3b disease were identified as independent prognosticators for 5-year outcomes. Based on these variables, we devised a scoring system that identified four distinct prognostic groups. The 5-year rates for patients with a score from 0 to 3 were as follows: loco-regional control, 80%/67%/47%/24% (P < 0.001); distant metastases, 13%/23%/55%/92% (P < 0.001); DFS, 74%/58%/28%/7% (P < 0.001); and disease-specific survival, 80%/64%/35%/7% (P < 0.001) respectively. CONCLUSIONS: The combined assessment of tumor and nodal SUV-max, genetic markers, and pathological node status may refine the prognostic stratification of OCSCC patients.

Factors impacting on discordance with treatment plan in head and neck cancer patients: a retrospective, population-based cohort study.

PURPOSE: The aims of this study were to identify the factors and reasons impacting discordance with the treatment plan in head and neck cancer (HNC) patients and compare the differences between the concordance group and the discordance group. METHODS: This secondary analysis was conducted from population-based data from Taiwan collected from January 1, 2016, to June 30, 2018. Logistic regression analysis was used to identify the factors related to discordance with the treatment plan. RESULTS: We examined 1095 HNC patients, 12.1% of whom were discordant with treatment. Patients with advanced cancer stage, old age, and treatment plans of best supportive care (BSC) or surgery combined with radiation (RT), chemotherapy (CT), or chemoradiation (CCRT) were more likely to have discordance with their treatment plan. Of the 133 patients who were discordant with their treatment plan, the top reasons were as follows: "patients or their family considered patients' poor physical condition (chronic disease or unstable systemic disease), difficulty in enduring any condition likely to cause physical discomfort from disease treatment," "inconvenient transportation," and "disease progression." CONCLUSIONS: Patients' cancer stage, age, and types of treatment plans recommended significantly influenced discordance with treatment plan. Poor physical condition was the major reason for discordance with the treatment plan. Patients in the concordance group were significantly more likely than those in the discordance group to be younger than 65 years, have less advanced cancer stage, and be recommended to receive surgery rather than any other regimen. Multidisciplinary team care can help patients make positive decisions about treatment.

Tumor Depth of Invasion (Tumor > 4 cm/Depth > 10 mm and Depth > 20 mm) and Through Cortex/Skin Invasion are Both Valid Criteria for Classifying Tumors as pT4a in AJCC 2018 Oral Cavity Cancer Staging System.

BACKGROUND: According to the AJCC third to seventh edition staging manuals (1988-2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018) introduced a depth of invasion (DOI) > 20 mm as a criterion for pT4a. Subsequently, a revision maintained that tumors > 4 cm with a DOI > 10 mm should be classified as pT4a. We sought to analyze the prognostic impact of the three distinct criteria identifying pT4a disease. METHODS: We examined 667 consecutive patients with pT3-4 buccal/gum/hard palate/retromolar SCC who underwent surgery between 1996 and 2016. pT1/pT2 (n = 108/359) disease were included for comparison purposes. RESULTS: The 5-year outcomes of patients with pT1/pT2/without (n = 406)/with tumor > 4 cm/DOI > 10 mm (n = 261), pT1/pT2/DOI ≤ 20 mm (n = 510)/> 20 mm (n = 157), and pT1/pT2/without (n = 305)/with through cortex/skin invasion (n = 362) were as follows: disease-specific survival (DSS), 98%/89%/79%/65%, p < 0.001, 98%/89%/78%/59%, p < 0.001, and 98%/89%79%/69%, p < 0.001; overall survival (OS), 90%/79%/63%/51%, p < 0.001, 90%/79%/63%/42%, p < 0.001, and 90%/79%/65%/52%, p < 0.001. In pT3-4 disease, a tumor > 4 cm/DOI > 10 mm was an independent adverse prognosticator for 5-year DSS rate, DOI > 20 mm was an independent adverse prognosticator for 5-year DSS and OS rates, whereas through cortex/skin invasion independently predicted 5-year OS rates. CONCLUSIONS: All of the three criteria (tumor > 4 cm/DOI > 10 mm, DOI > 20 mm, and through cortex/skin invasion) identify high-risk patients, which should be reflected in further revisions of pT4a classification in OCSCC.

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

BACKGROUND: Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. METHODS: Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. RESULTS: Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). CONCLUSIONS: Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018;124:2948-55. © 2018 American Cancer Society.

Clinical utility of simultaneous whole-body 18F-FDG PET/MRI as a single-step imaging modality in the staging of primary nasopharyngeal carcinoma.

PURPOSE: Both head and neck magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) play a crucial role in the staging of primary nasopharyngeal carcinoma (NPC). In this study, we sought to prospectively investigate the clinical utility of simultaneous whole-body 18F-FDG PET/MRI for primary staging of NPC patients. METHODS: We examined 113 patients with histologically confirmed NPC who underwent pretreatment, simultaneous whole-body PET/MRI and PET/CT for primary tumor staging. The images obtained with the different imaging modalities were interpreted independently and compared with each other. RESULTS: PET/MRI increased the accuracy of head and neck MRI for assessment of primary tumor extent in four patients via addition of FDG uptake information to increase the conspicuity of morphologically subtle lesions. PET/MR images were more discernible than PET/CT images for mapping tumor extension, especially intracranial invasion. Regarding the N staging assessment, the sensitivity of PET/MRI (99.5%) was higher than that of head and neck MRI (94.2%) and PET/CT (90.9%). PET/MRI was particularly useful for distinguishing retropharyngeal nodal metastasis from adjacent nasopharyngeal tumors. For distant metastasis evaluation, PET/MRI exhibited a similar sensitivity (90% vs. 86.7% vs. 83.3%), but higher positive predictive value (93.1% vs. 78.8% vs. 83.3%) than whole-body MRI and PET/CT, respectively. CONCLUSIONS: For tumor staging of NPC, simultaneous whole-body PET/MRI was more accurate than head and neck MRI and PET/CT, and may serve as a single-step staging modality.

To do or not to do: salvage management for hypopharyngeal cancer after chemoradiation therapy.

PURPOSES: The management of recurrent hypopharyngeal cancer after primary curative-intent radiation or chemoradiation therapy is inconclusive. The benefit of salvage surgery may be reduced by its high complication rate. The improvement of medical care modalities may change the survival after management for loco-reginal recurrences. The present study aims to determine the role of salvage surgery. METHODS: From December 2007 to November 2013, 46 patients with recurrent hypopharyngeal squamous cell carcinoma (HPSCC) after radiation or chemoradiation therapy and without double cancers were recruited. Two year loco-regional failure and overall survival were analyzed and compared between failure patterns. RESULTS: Five-year survival was 24% in patients after loco-regional recurrences. Those who received salvage surgery for loco-regional recurrences had significantly better survival (P < 0.001). Among patients with salvage surgery, 2-year overall survival was significantly higher in recurrent (n = 11) than persistent (n = 24) disease (90 vs 38%, P = 0.006). CONCLUSIONS: Salvage surgery provides better oncologic outcomes in patients with HPSCC, especially for patients with recurrences after 6 months since completion of primary radiation or chemoradiation. The present data of outcomes can be provided for pretreatment consultation for loco-regional recurrent hypopharyngeal cancers.

Clinical Outcomes in pT4 Tongue Carcinoma are Worse than in pT3 Disease: How Extrinsic Muscle Invasion Should be Considered?

BACKGROUND: The identification of extrinsic tongue muscle invasion in oral cavity cancer remains challenging. Notably, the most recent American Joint Committee on Cancer (AJCC 2017, 8th edition) staging manual indicates that extrinsic muscle invasion does not lead to the diagnosis of a T4 tumor. Because this approach carries the risk of tumor downstaging, we compared the clinical outcomes of patients with oral tongue squamous cell carcinoma (SCC) staged as pT3 vs. pT4 according to the AJCC 2010, 7th edition criteria. METHODS: We retrospectively examined the records of consecutive patients with pT3 (n = 135) and pT4 (n = 68) tongue SCC who underwent radical surgery. Of the 68 pT4 tongue SCC, 63 (93%) had extrinsic muscle involvement alone. The 5-year locoregional control (LRC), distant metastasis (DM), and disease-free survival (DFS) rates served as outcome measures. RESULTS: Compared with pT3 tongue SCC, pT4 patients presented significantly more frequently with pN2 disease, extranodal extension, poor tumor differentiation, tumor depth >15 and >20 mm, margin status ≤4 mm, perineural invasion, vascular invasion, and were more frequently treated with surgery plus concurrent chemoradiotherapy. Less favorable 5-year outcomes were observed in patients with pT4 than pT3 tumors (LRC 50 vs. 75%, p < 0.001; DM 27 vs. 14%, p = 0.013; DFS 43 vs. 69%, respectively, p < 0.001). We identified pT4 disease (vs. pT3) as an independent adverse prognostic factor for LRC and DFS. CONCLUSIONS: We suggest classifying patients with tongue SCC and extrinsic muscle invasion as having pT4 disease.

Clinical Outcomes of Taiwanese Patients with cT4 Oral Cavity Squamous Cell Carcinoma: Toward the Identification of the Optimal Initial Treatment Approach for cT4b Patients.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.

Clinical impact of PET/CT imaging after adjuvant therapy in patients with oral cavity squamous cell carcinoma.

PURPOSE: This single-center retrospective study of prospectively collected data was aimed at comparing the clinical outcomes of positron emission tomography/computed tomography (PET/CT) for patients with oral cavity squamous cell carcinoma (OSCC) with symptomatic recurrences identified by PET/CT imaging following adjuvant therapy (Group A) versus those of cases with asymptomatic recurrences diagnosed through periodic post-adjuvant therapy PET/CT surveillance (Group B). We also sought to establish the priority of salvage therapy in the two study groups. METHODS: We identified 111 patients with advanced resected OSCC who developed recurrences following adjuvant therapy (51 in Group A and 60 in Group B). Histopathology served as the gold standard for recurrent lesions. The impact of post-adjuvant therapy PET/CT surveillance was examined with Kaplan-Meier curves and Cox proportional hazards regression models. RESULTS: The 2-year DSS and OS rates were marginally or significantly higher in Group B than in Group A (P = 0.073 and P = 0.025, respectively). Time-dependent ROC curve analysis demonstrated that the optimal cutoff values for time to positive PET/CT findings in relation to OS were 12 months for Group A and 9 months for Group B, respectively. Independent risk factors identified in multivariate analyses were used to devise two prognostic scoring systems for 2-year DSS and OS in each study group (all P < 0.001). CONCLUSIONS: Scheduled periodic PET/CT surveillance is a valuable tool for early detection of recurrent lesion(s) in asymptomatic OSCC patients who bear risk factors for disease recurrence. The presence of clinical symptoms and a short time to positive PET/CT findings were adverse prognostic factors for clinical outcome in patients with advanced OSCC. The priority of salvage therapy is discussed in each patient subgroup according to the devised prognostic scoring systems.

EGFR copy number alterations in primary tumors, metastatic lymph nodes, and recurrent and multiple primary tumors in oral cavity squamous cell carcinoma.

BACKGROUND: The EGFR and downstream signaling pathways play an important role in tumorigenesis in oral squamous cell carcinoma (OSCC). Gene copy number alteration is one mechanism for overexpressing the EGFR protein and was also demonstrated to be related to lymph node metastasis, tumor invasiveness and perineural invasion. Therefore, we hypothesized that EGFR gene copy number alteration in the primary tumor could predict amplification in recurrent tumors, lymph node metastatic foci or secondary primary tumors. METHODS: We recruited a group of newly diagnosed OSCC patients (n = 170) between Mar 1997 and Jul 2004. Metastatic lymph nodes were identified from neck dissection specimens (n = 57). During follow-up, recurrent lesions (n = 41) and secondary primary tumors (SPTs, n = 17) were identified and biopsied. The EGFR gene amplifications were evaluated by fluorescence in situ hybridization (FISH) assay in primary tumors, metastatic lymph nodes, recurrences and SPTs. RESULTS: Of the 170 primary OSCCs, FISH showed low EGFR amplification/polysomy in 19 (11.4%) patients and amplification in 33 (19.8%) patients. EGFR gene amplification was related to lymph node metastasis (χ2 trend test: p = 0.018). Of 57 metastatic lymph nodes, nine (15.8%) had EGFR polysomy and 14 (24.6%) had EGFR gene amplification. The concordance rate of EGFR gene copy number in primary tumors and lymph node metastasis was 68.4% (McNemar test: p = 0.389). Of 41 recurrent tumors, five (12.2%) had EGFR polysomy and five (12.2%) had gene amplification. The concordance rate of EGFR gene copy number between primary tumors and recurring tumors was 65.9% (McNemar test: p = 0.510). The concordance rate between primary tumors and SPTs was 70.6%. EGFR amplification in either primary tumors, metastatic lymph nodes or recurrent tumors had no influence on patient survival. CONCLUSION: We can predict two-thirds of the EGFR gene copy number alterations in lymph node metastasis or recurrent tumors from the analysis of primary tumors. For OSCC patients who are unable to provide lymph node or recurrent tumor samples for EGFR gene copy number analysis, examining primary tumors could provide EGFR clonal information in metastatic, recurrent or SPT lesions.

The second-time flap from the previously used anterior thigh donor site for head and neck microsurgical reconstruction.

BACKGROUND: Multiple free tissue transfer from the same donor site is not well described for microsurgical head and neck reconstruction. METHODS: Between (8/2011 and 11/2012), 103 patients received 103 free ALT flaps for head and neck reconstruction; flaps were called first-time ALT flaps. Intra-operative findings were used to assess the presence of a favorable anatomy for a future second flap from the same donor site. And, between 9/2009 and 12/2013, second-time flaps from previously used anterior thighs were attempted either freely or guided by the intra-operative data from the previous surgery. RESULTS: A favorable anatomy for a future second-time flap was noted in (n: 96/103). Future second-time flaps were ALT, AMT, and TFL flaps (n: 32, n: 91, n: 96, respectively). The second-time flap was attempted (n: 11) and was successful (n: 8, 72.7%). Harvested second-time flaps were (5 ALT, 2 AMT, 1TFL). All flaps survived. The donor site was closed primarily (n: 6) and skin grafted (n: 2). CONCLUSION: Thorough exploration of the anatomy of the anterior thigh during the first-time ALT flap surgery with detailed documentation in addition to meticulous surgery are essential for success. The proposed concept limits morbidity to one site, and serves as an alternative donor site or a life-boat.