Neoadjuvant immunochemotherapy for locally advanced resectable oral squamous cell carcinoma: a prospective single-arm trial (Illuminate Trial).

BACKGROUND: Locally advanced oral squamous cell carcinoma (LAOSCC) is associated with a high rate of recurrence and poor survival. Given the recent successes of neoadjuvant immunochemotherapy (NAICT) in solid tumors, it is promising to use this treatment modality to achieve a better pathological response and improve the survival of LAOSCC, and clinical evidence is needed to assess its safety and efficacy. PATIENTS AND METHODS: A prospective trial of NAICT with toripalimab (PD-1 inhibitor) and albumin paclitaxel/cisplatin (TTP) was conducted in patients with clinical stage III and IVA OSCC. Intravenous albumin paclitaxel (260 mg/m 2 ), cisplatin (75 mg/m 2 ), and toripalimab (240 mg) were given in sequence on day 1 of each 21 day cycle for two cycles, followed by radical surgery and risk-adapted adjuvant (chemo)radiotherapy. The primary endpoints were safety and major pathological response (MPR). Targeted next generation sequencing and multiplex immunofluorescence were performed to assess clinical molecular characteristics and the tumor immune microenvironment in the pre-NAICT and post-NAICT tumor samples. RESULTS: Twenty patients were enrolled. NAICT was well-tolerated with a low incidence of grades 3-4 adverse events in three patients. The completion rates of NAICT and subsequent R0 resection were 100%. The MPR rate was 60%, including a 30% pathological complete response. MPR was achieved in all four patients with a combined positive score of PD-L1>10. The density of tertiary lymphatic structure in post-NAICT tumor samples predicted the pathological response to NAICT. During the median 23-month follow-up, the disease-free survival was 90%, and the overall survival was 95%. CONCLUSIONS: NAICT with the TTP protocol in LAOSCC is feasible and well tolerated, with a promising MPR and no obstruction on subsequent surgery. This trial is supportive of further randomized trials using NAICT in LAOSCC.

Efficacy and feasibility of Apatinib and S-1 as a novel oral induction therapy in locally advanced head and neck squamous cell carcinoma: an exploratory phase 2 open-label, single-arm trial.

Objectives: The current standard nonsurgical treatment for locally advanced head and neck squamous cell cancer (LA-HNSCC) is concomitant chemoradiotherapy (CRT). Neoadjuvant chemotherapy combined with CRT has been explored in HNSCC patients and is an acceptable strategy. However, the occurrence of adverse events (AEs) restricts its application. We conducted a clinical study to explore the efficacy and feasibility of a novel induction therapy with orally administered apatinib and S-1 in LA-HNSCC. Materials and methods: This nonrandomized, single-arm, prospective clinical trial included patients with LA-HNSCCs. The eligibility criteria included histologically or cytologically confirmed HNSCC, with at least one radiographically measurable lesion detected by magnetic resonance imaging (MRI) or computerized tomography (CT) scan, age 18-75 years, and a diagnosis of stage III to IVb according to the 7th edition of the American Joint Committee of Cancer (AJCC). Patients received induction therapy with apatinib and S-1 for three cycles (3 weeks/cycle). The primary endpoint of this study was the objective response rate (ORR) to induction therapy. The secondary endpoints included progression-free survival (PFS), overall survival (OS), and AEs during induction treatment. Results: From October 2017 to September 2020, 49 patients with LA-HNSCC were screened consecutively and 38 were enrolled. The median age of the patients was 60 years (range, 39-75). Thirty-three patients (86.8%) had stage IV disease according to the AJCC staging system. The ORR after induction therapy was 97.4% (95% confidence interval [CI]: 86.2%-99.9%). the 3-year OS rate was 64.2% (95% CI: 46.0%-78.2%) and 3-year PFS was 57.1% (95% CI: 40.8%-73.6%). The most common AEs during induction therapy were hypertension and hand-foot syndrome, which were manageable. Conclusion: Apatinib combined with S-1 as novel induction therapy for LA-HNSCC patients resulted in a higher-than-anticipated ORR and manageable adverse effects. With the associated safety profile and preferable oral administration route, apatinib combined with S-1 is an attractive exploratory induction regimen in outpatient settings. However, this regimen failed to show a survival benefit. Clinical trial registration: https://clinicaltrials.gov/show/NCT03267121, identifier NCT03267121.

Adjuvant PD-1 antibody in recurrent, previously irradiated oral cavity cancer treated with salvage surgery.

Objectives: The role of re-irradiation after salvage surgery for recurrent oral cavity cancer (OCC) is controversial. We evaluated the efficacy and safety of adjuvant toripalimab (PD-1 antibody) in this patient setting. Materials and methods: In this phase II study, patients after salvage surgery with OCC occurring in an area of previously irradiated were enrolled. Patients received toripalimab 240 mg once every 3 weeks for 12 months, or combined with S-1 orally for 4-6 cycles. The primary endpoint was 1-year progression-free survival (PFS). Results: Between April 2019 and May 2021, 20 patients were enrolled. Sixty percent patients had ENE or positive margins, 80% were restaged as stage IV, and 80% were previously treated with chemotherapy. The 1-year PFS and overall survival (OS) were 58.2%, and 93.8%, respectively, for patients with CPS ≥ 1, which was significantly better than those of the real-world reference cohort (p = 0.001 and 0.019). No grade 4-5 toxicities were reported, and only one patient experienced grade 3 immune related adrenal insufficiency and discontinued treatment. The 1-year PFS and OS were significantly different for patients with CPS < 1, CPS 1-19 and CPS ≥ 20 (p = 0.011 and 0.017, respectively). The peripheral blood B cell proportion was also correlated with PD in 6 months (p = 0.044). Conclusion: Adjuvant toripalimab or combine with S-1 after salvage surgery showed improved PFS compared with a real-world reference cohort in recurrent, previously irradiated OCC, and favorable PFS were observed in patients with a higher CPS and peripheral B cell proportion. Further randomized trials are warranted.

Can adjuvant radiotherapy be omitted for oral cavity cancer patients who received neoadjuvant therapy and surgery? A retrospective cohort study.

BACKGROUND: Surgery and postoperative adjuvant therapy comprise the standard treatment for locally advanced resectable oral squamous cell carcinoma (LAROSCC), while preoperative neoadjuvant therapy is being explored without sufficient confirmation of improved survival. De-escalation regimens after neoadjuvant therapy, such as those omitting adjuvant radiotherapy, may provide comparable or better outcomes, suggesting rigorous assessment of adjuvant therapy outcomes is needed in LAROSCC patients. The authors thus performed this retrospective study in LAROSCC patients who received neoadjuvant therapy and surgery, to compare the outcomes for overall survival (OS) and locoregional recurrence-free survival (LRFS) between the adjuvant radiotherapy (radio) and nonradiotherapy (nonradio) cohorts. MATERIALS AND METHODS: Patients diagnosed with LAROSCC who received neoadjuvant therapy and surgery were enrolled and divided into radio and nonradio cohorts to determine whether adjuvant radiotherapy could be omitted after neoadjuvant therapy and surgery. RESULTS: From 2008 to 2021, 192 patients were enrolled. No significant differences were found in OS or LRFS between the radio and nonradio patient cohorts. The 10-year estimated OS rates were 58.9 versus 44.1% in radio versus nonradio cohorts, while 10-year estimated LRFS rates were 55.4 versus 48.2%, respectively. For clinical stage III patients, 10-year OS rates were 62.3 versus 62.6% (radio vs. nonradio), and estimated 10-year LRFS rates were 56.5 versus 60.7% (radio vs. nonradio). Multivariate Cox regression modeling of postoperative variables showed pathologic response of primary tumor and pathologic regional lymph nodes staging were associated with survival, while the adjuvant radiotherapy exposure was not included in the model due to nonsignificance. CONCLUSION: These findings support further prospective evaluation of adjuvant radiotherapy omission, and suggest that de-escalation trials are warranted for LAROSCC surgery patients who received neoadjuvant therapy.

Combined all-trans retinoic acid with low-dose apatinib in treatment of recurrent/metastatic head and neck adenoid cystic carcinoma: A single-center, secondary analysis of a phase II study.

BACKGROUND: Treatment options are limited for recurrent/metastatic adenoid cystic carcinoma of the head and neck (R/M ACCHN). We aimed to evaluate the preliminary results of the efficacy and safety of all-trans retinoic acid (ATRA) combined with low-dose apatinib in patients with R/M ACCHN according to a secondary analysis of a phase II study. METHODS: Patients from a phase II study (NCT02775370) who orally administered 500 milligram (mg) apatinib daily until treatment-related adverse events (AEs) intolerance or progression occurred were eligible for inclusion. Patients were further treated with combination therapy of ATRA (25 mg/m2 /day) and apatinib (250 mg/day) between March 2019 and October 2021 until progression of disease (PD). RESULTS: A total of 16 patients were included with nine (56.3%) males and aged 35-69 years old. All recruited patients previously received anti-angiogenic therapy then withdrew due to toxicities or progression occurred. The objective response rate (ORR) and disease control rate (DCR) were 18.8% and 100%, respectively. During a median follow-up of 23.9 months (range:17.8-31.7 months), 11 (68.8%) patients developed PD and one of them died in 20.9 months. The median of progression-free survival (PFS) was 16.3 months (95% CI: 7.2-25.4 months), and the 6-month, 12-month, and 24-month PFS rates were 100%, 81.3%, and 33.3%, respectively. The grade 3 adverse events were albuminuria (n = 2, 12.5%) and hand-foot syndrome (n = 1, 6.25%). CONCLUSION: All-trans retinoic acid combined with low-dose apatinib might be a potential efficacy therapeutic option for patients with R/M ACCHN. This finding will be further confirmed by our registered ongoing trial, the APLUS study (NCT04433169).

A pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma.

Novel neoadjuvant therapy regimens are warranted for oral squamous cell carcinoma (OSCC). In this phase I trial (NCT04393506), 20 patients with locally advanced resectable OSCC receive three cycles of camrelizumab (200 mg, q2w) and apatinib (250 mg, once daily) before surgery. The primary endpoints are safety and major pathological response (MPR, defined as ≤10% residual viable tumour cells). Secondary endpoints include 2-year survival rate and local recurrence rate (not reported due to inadequate follow-up). Exploratory endpoints are the relationships between PD-L1 combined positive score (CPS, defined as the number of PD-L1-stained cells divided by the total number of viable tumour cells, multiplied by 100) and other immunological and genomic biomarkers and response. Neoadjuvant treatment is well-tolerated, and the MPR rate is 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃10 achieve MPR. Post-hoc analysis show 18-month locoregional recurrence and survival rates of 10.5% (95% CI: 0%-24.3%) and 95% (95% CI: 85.4%-100.0%), respectively. Patients achieving MPR show more CD4+ T-cell infiltration than those without MPR (P = 0.02), and decreased CD31 and ɑ-SMA expression levels are observed after neoadjuvant therapy. In conclusion, neoadjuvant camrelizumab and apatinib is safe and yields a promising MPR rate for OSCC.

EGFR Mutation and 11q13 Amplification Are Potential Predictive Biomarkers for Immunotherapy in Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers. The treatment of HNSCC remains challenging despite recent progress in targeted therapies and immunotherapy. Research on predictive biomarkers in clinical settings is urgently needed. Methods: Next-generation sequencing analysis was performed on tumor samples from 121 patients with recurrent or metastatic HNSCC underwent sequencing analysis. Clinicopathological information was collected, and the clinical outcomes were assessed. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and cox regression model was used to conduct multivariate analysis. Fisher's exact tests were used to calculate clinical benefit. A p value of less than 0.05 was designated as significant (p < 0.05). Results: Chromosome 11q13 amplification (CCND1, FGF3, FGF4, and FGF19) and EGFR mutations were significantly associated with decreased PFS and no clinical benefits after treatment with a programmed death 1 (PD-1) inhibitor. The same results were found in the combined positive score (CPS) ≥ 1 subgroup. In patients who were treated with an EGFR antibody instead of a PD-1 inhibitor, a significant difference in PFS and clinical benefits was only observed between patients with CPS ≥ 1 and CPS < 1. Conclusion: Chromosome 11q13 amplification and EGFR mutations were negatively correlated with anti-PD-1 therapy. These markers may serve as potential predictive biomarkers to identify patients for whom immunotherapy may be unsuitable.

The Immune Landscape of Chinese Head and Neck Adenoid Cystic Carcinoma and Clinical Implication.

Novel systemic agents and effective treatment strategies for recurrence adenoid cystic carcinoma (ACC) of the head and neck are still worthy of further exploration. Here, we analyzed the mutations and expression profiles of 75 Chinese ACC patients, characterized the prognostic value of the immune signature for recurrence or distant metastasis, and explored the potential of immunotherapeutic biomarkers in ACC. In general, MYB fusion and somatic mutations accounted for a high proportion, which was 46.7% (35/75). ACCs displayed an overall low mutation burden and lack of programmed cell death ligand-1 (PD-L1) expression. The antigen-presenting machinery (APM) expression score and immune infiltration score (IIS) were the lowest among ACC patients, compared with other cancer types. For 61 primary cases, the locoregional recurrence-free survival (LRRFS) was statistically significantly correlated with the IIS [univariate analysis; hazard ratio (HR) = 0.32; 95% CI, 0.11-0.92; p = 0.035] and T-cell infiltration score (TIS) (univariate analysis; HR = 0.33; 95% CI, 0.12-0.94; p = 0.037]. Patients with lower IIS (log-rank p = 0.0079) or TIS (log-rank p = 0.0079) had shorter LRRFS. Additionally, solid pattern was also a prognostic factor related to locoregional recurrence, whereas postoperative radiotherapy (PORT) exerted its beneficial effects. We further evaluated the pretreatment immune profile of five ACC patients treated with PD-1 inhibitors. Patients who responded to camrelizumab or pembrolizumab observed elevated APM and TIS, compared with patients with progressive disease. Our study highlights the immune infiltration pattern and messenger RNA (mRNA) signatures of Chinese ACC patients, which has the potential value for prognosis and immunotherapy.

Apatinib in patients with recurrent or metastatic adenoid cystic carcinoma of the head and neck: a single-arm, phase II prospective study.

BACKGROUND: Apatinib, a vascular endothelial growth factor receptor (VEGFR) blocker, has demonstrated encouraging antitumor activities and tolerable toxicities in various cancer types. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) carries a poor prognosis, and treatment options are currently limited. This study was conducted to explore the antitumor activity and safety of apatinib in patients with R/MACCHN. METHODS: In this phase II single-arm, prospective study, patients aged 15-75 years with incurable R/MACCHN received apatinib at a 500 mg dose once daily until intolerance or progression occurred. The primary endpoint was the 6-month progression-free survival (PFS) rate based on RECIST version 1.1. The secondary endpoints included response rate, overall survival (OS), and safety. Efficacy was assessed in all dosed patients with at least one post-baseline tumor assessment. RESULTS: Among 68 patients treated with apatinib, 65 were evaluable for efficacy analysis, with a median follow-up time of 25.8 months. The 6-month, 12-month, and 24-month PFS rates were 92.3% [95% confidence interval (CI): 83-97.5%], 75.2% (95% CI: 61.5-84.0%) and 44.7% (95% CI: 32.3-57.5%), respectively. The objective response rate (ORR) and disease control rate (DCR), as assessed by investigators, were 46.2% (95% CI: 33.7-59.0%) and 98.5% (95% CI: 91.7-100.0%), respectively. The median duration of response was 17.7 months [interquartile range (IQR) 14.0-20.9]. The 12-month and 24-month OS rates were 92.3% (95% CI: 83.0-97.5%) and 82.3% (95% CI: 70-90.4%), respectively. The most common adverse events of grades 3-4 were hypertension (5.9%), proteinuria (9.2%), and hemorrhage (5.9%). One patient developed a fatal hemorrhage. CONCLUSION: An encouraging PFS, a high ORR, and a manageable safety profile were observed in this study. It seems that the administration of apatinib in R/MACCHN is likely to have a clinically meaningful therapeutic benefit and warrants further investigation.This study was prospectively registered in ClinicalTrials.gov (NCT02775370; date of registration: 17 May 2016; date of first patient enrollment: 25 May 2016).

A Phase 2 Trial of Chemoradiation Therapy Using Weekly Docetaxel for High-Risk Postoperative Oral Squamous Cell Carcinoma Patients.

PURPOSE: To evaluate the efficacy and safety of postoperative concurrent chemoradiation therapy using weekly docetaxel in patients with high-risk oral squamous cell carcinoma (OSCC). METHODS AND MATERIALS: This is a prospective single-arm study from a single institute in Shanghai Ninth People's Hospital, Shanghai, China. Patients with locally stage III to IV OSCC who underwent radical surgery with at least 1 high-risk feature were enrolled for the study. High-risk features evaluated included (1) pathologically confirmed positive or close margins in the primary site or extracapsular nodal extension; (2) histologic involvement of ≥2 regional lymph nodes; and (3) locoregional recurrent OSCC (after initial surgery alone) treated with salvage surgery with curative intent. Docetaxel was administered at a dose of 20 mg/m2 concurrently with postoperative radiation therapy (total dose 60-66 Gy). The primary outcome was 2-year disease-free survival (DFS). Secondary endpoints included 2-year locoregional progress-free survival, 2-year overall survival (OS), and toxicities. RESULTS: From March 2016 to February 2018, 91 patients (59 males, 32 females) were recruited. Median age was 59 years (range, 26-70). All patients were included in final analysis. Fifty-eight patients (63.7%) completed the 6 planned cycles of docetaxel, and all patients completed postoperative radiation therapy. With a median follow-up of 24 months, the 2-year DFS and OS were 75.3% (95% confidence interval, 65.7%-84.2%) and 82.4% (95% confidence interval, 73.0%-89.6%), respectively. Patterns of failure were 13 local recurrences, 2 regional lymph nodes recurrences, and 8 distant failures. Seven patients (7.7%) were recorded as having grade 3 oral cavity mucositis. Two patients had grade 3 hypersensitivity reaction. No other grade 3 or higher adverse events, including hematologic toxicities, were observed. CONCLUSIONS: The addition of low-dose weekly docetaxel with concurrent radiation therapy is a tolerable regimen with favorable DFS and OS in patients with high-risk, resected OSCC.

Long-term results of elective mucosal irradiation for head and neck cancer of unknown primary in Chinese population: The EMICUP study.

OBJECTIVE: Controversy still exists regarding the volume of radiation for head and neck cancer of unknown primary (HNCUP). Theoretically, elective mucosal irradiation (EMI) should achieve a balance between survival and toxicity. This prospective study was conducted to evaluate the long-term benefit of EMI in Chinese HNCUP patients. METHODS: A phase II, single-arm trial was performed at two centers in China. HNCUP patients with pathologically confirmed metastatic squamous cell carcinoma or poorly differentiated carcinoma were enrolled. Patients with metastatic lymph nodes limited to level IV and/or the supraclavicular fossa were excluded. The EMI approach was specifically customized to Chinese patients by differentiating HNCUP as putative nasopharyngeal carcinoma (NPC) or non-putative NPC. The primary endpoint was 3-year mucosal recurrence-free survival (MRFS). RESULTS: A total of 48 patients were enrolled between 02/02/2010 and 08/01/2018; 46 patients were analyzed, including 24 putative NPC and 22 non-putative NPC patients. No primary recurrence was observed during a median follow-up period of 70 months, and only 1 patient experienced out of field recurrence in the contralateral neck. The 3-year MRFS was 90.6% (95%CI: 76.4%-96.4%). The 5-year MRFS, regional-recurrence free survival (RRFS) and overall survival (OS) were 90.6% (95%CI: 76.4%-96.4%), 86.0% (95%CI: 71.1%-93.7%), and 90.6% (95%CI: 76.4%-96.4%), respectively. No grade 4 acute or late toxicities occurred, and the most frequent grade 3 acute toxicity was oral mucositis (45.7%). CONCLUSION: To the best of our knowledge, this is the first prospective study to evaluate the long-term outcomes of EMI in Chinese HNCUP patients. Excellent MRFS and OS rates were observed. Further randomized studies are warranted.

Effect of oral supplements on the nutritional status of nasopharyngeal carcinoma patients undergoing concurrent chemotherapy: A randomized controlled Phase II trial.

OBJECTIVES: The objectives of this study were to prospectively compare individualized dietary counseling with or without oral nutritional supplements (ONSs) in nasopharyngeal carcinoma (NPC) patients undergoing concurrent chemoradiotherapy (CCRT) in a Phase II, randomized trial. MATERIALS AND METHODS: Between June 2014 and August 2016, Stage II-IVb NPC patients were randomly enrolled. The primary endpoint was change in body weight between during CCRT, and the secondary endpoints were change in body mass index (BMI) and fat-free mass index (FFMI). RESULTS: Fifty-two patients were randomized; 19 patients in the control group and 23 in the ONS group were eligible for analysis. Weight, BMI, and body composition parameters significantly decreased from baseline to week 6. FFMI was significantly better in patients with ONS intake >2/3 planed than the control group (P = 0.028). Weight and BMI maintenance was slightly better in patients with total intake >2/3 planed (P = 0.170 and P= 0.229, respectively). The mean Patient-Generated Subjective Global Assessment score was also better in the ONS group at the end of CCRT (P = 0.053). CONCLUSIONS: ONSs with individualized dietary counseling may be beneficial in patients with enough intake, and further prospective studies with large groups of patients are warranted.

Longitudinal Body Composition Changes and the Importance of Fat-Free Mass Index in Locally Advanced Nasopharyngeal Carcinoma Patients Undergoing Concurrent Chemoradiotherapy.

AIM: This was a prospective investigation of longitudinal body composition changes in patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy (CCRT) and a comparison of the Patient-Generated Subjective Global Assessment (PG-SGA) and the ESPEN (European Society for Clinical Nutrition and Metabolism) diagnostic criteria (EDC) as evaluation methods. METHODS: All patients received standard CCRT according to 2 centers' current practices. Body composition parameters were determined by bioelectrical impedance analysis and obtained weekly from baseline until the end of treatment. The nutritional status of all patients was evaluated by the PG-SGA and EDC. RESULTS: Forty-eight patients were eligible for analysis. Most body composition parameters, including body cell mass, fat mass, fat-free mass, and skeletal mass, as well as body weight, body mass index, and PG-SGA score, significantly decreased during CCRT ( P = .00). The PG-SGA was shown to have better sensitivity than the EDC; however, the 2 different evaluation methods were found to have a perfect concordance at Week 4 and Week 6 (κ = 0.91 and 0.96, P = .00 and .00, respectively). Pearson correlation analyses showed that fat-free mass index and body weight were positively correlated with global quality of life score ( r = 0.81, P = .00; r = 0.78, P = .00, respectively). CONCLUSIONS: This study has shown that body composition parameters, especially fat-free mass index, are valuable for diagnosing malnutrition in patients with nasopharyngeal carcinoma receiving CCRT. We recommend that these bioelectrical impedance analysis techniques should be increasingly implemented in nutritional assessments.

A feasibility and safety study of concurrent chemotherapy based on genetic testing in patients with high-risk salivary gland tumors: Preliminary results.

BACKGROUND: This prospective study was conducted to evaluate the feasibility and safety of customized chemotherapy regimens based on the gene characteristics of salivary gland tumors. METHODS: Patients were enrolled with histologically confirmed intermediate or high grade, stage T3-4, N1-3 disease, and T1-2, N0 patients with a close (≤1 mm) or microscopically positive surgical margin were also enrolled in the study. All patients received radical surgery and postoperative concurrent chemoradiotherapy. To evaluate the responsiveness of therapies, the chemotherapy regimen was based on gene targets, ß-tubulin III, ABCB1, STMN1, and CYP1B1 (for docetaxel) and TYMS (for pemetrexed). The primary endpoints were treatment compliance and acute toxicities. RESULTS: A total of 20 patients were enrolled between September 2013 and January 2016. The median age was 46 years (range: 23-70 years). Genetic testing showed that 8 patients may have been sensitive to docetaxel, 5 patients may have been sensitive to pemetrexed, and 7 patients sensitive to either docetaxel or pemetrexed. All patients received the full dose of radiation. A total of 19 patients (95%) completed 2 cycles of concurrent chemotherapy (CCT). One patient treated concurrently with pemetrexed experienced grade 3 neutropenia. Three patients experienced grade 3 oral mucositis, and 2 patients experienced grade 3 dermatitis. CONCLUSION: Our study demonstrated that a CCT selecting method based on the gene targets associated with drug sensitivity was clinically feasible and safe. Further studies enrolled more patients with longer follow-up times are needed to confirm the clinical efficacy of this CCT selecting method.

Tailored multimodality therapy guided by a two-step decision making process for head-and-neck cancer of unknown primary.

BACKGROUND: There is no consensus on the treatment of head-and-neck cancer of unknown primary (HNCUP). The objective of this study is to report our single institution's experience of a tailored multimodality therapy guided by a two-step decision making process. MATERIALS AND METHODS: From January 2007 to November 2013, 92 consecutive patients of HNCUP were treated. 77 patients were treated according the process above, 24 were treated by radiotherapy to the nasopharyngeal site, 7 received neck dissection and radiotherapy to other putative mucosal site, 30 were treated by neck dissection alone, and 16 received neck dissection followed by radiotherapy to the neck. SPSS 20.0 software was used for statistical analysis. RESULTS: After a median follow-up of 34 months, the 3-year overall survival rate was 84.5%. The 3-year mucosal control rate, neck control rate, distant metastasis-free survival rate and disease-free survival rate were 80.9%, 76.2%, and 92.0%, respectively. Of the 24 patients treated as putative nasopharyngeal carcinoma, no primary emerged from any site. Primary tumor emerged in 14 patients, and no primary emerged in the 31 patients treated with putative site radiation (3-year mucosal control rate: 100% vs. 67.9%, p = 0.010). Of the 46 patients treated with neck dissection with/without postoperative radiation, 14 developed neck recurrence, and patients without postoperative radiation suffered more ipsilateral neck recurrence. CONCLUSIONS: The two-step decision-making process seem to be reasonable in treating Chinese HNCUP patients. However, this results need to be prospectively validated.

Multi-modality management for loco-regionally advanced laryngeal and hypopharyngeal cancer: balancing the benefit of efficacy and functional preservation.

The 5-year overall survival (OS) of loco-regionally advanced laryngeal and hypopharyngeal carcinoma (LA-LHC) has declined over the past two decades following the wide application of non-surgical approaches. We aimed to define the new role of open surgery combined with adjuvant chemoradiotherapy in the treatment of LA-LHC for improving survival while maintaining a functional larynx. In the current study, 90 LA-LHC patients treated with open surgery followed by postoperative RT/CRT in our institute from May 2005 to December 2012 were retrospectively analyzed. OS, disease-free survival (DFS), loco-regional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were calculated, and prognostic factors were analyzed. Functional larynx preservation results were evaluated according to the head and neck quality of life (QoL) Scale. With a median follow-up period of 37 months, the 3- and 5-year OS, DFS, LRFFS and DMFS were 71.3, 63.7, 85.9, 73.7 and 55.9, 53.0, 81.6, 71.9 %, respectively. Vascular embolism and extracapsular extension (ECE) of the lymph nodes were prognostic factors for poorer OS (p = 0.045 and 0.046, respectively). Vascular embolism was the only prognostic factor for poorer DMFS (p = 0.005). Patients who underwent a conservative partial laryngectomy (CPL) experienced a higher QoL in the domains of speech, swallowing and emotion. Functional larynx preservation was achieved in 36/45 patients (80 %) who received CPL. The results of our study demonstrated that CPL followed by adequate adjuvant therapy could achieve superior oncological results compared with non-surgical approaches in LA-LHC patients while also maintaining satisfactory functional larynx in a majority of patients.