Concomitant Chemoradiotherapy for Advanced Head and Neck Cancer

Head and neck cancer is mostly curable in the early stages byeither surgery or radiotherapy alone, but the control rate foradvanced stages is low, even with combined surgery and postoperativeradiotherapy. From September, 1990, to January, 1992, 35 patientswith locoregionally advanced head and neck cancers were enteredin a prospective study of concomitant chemoradiotherapy. Thirty-threecompleted the treatment. There were 29 males and four femaleswith a median age of 53 years. All except one patient were instage IV. Radiotherapy was delivered using a telecobalt unitand by conventional fractionation (1.8 Gy/fraction, 5 fractions/wk).Chemotherapy with cisplatin (10 mg/m²/day, daily, days 1-5)and 5-FU (500 mg/m²/day continuously infused for five days)was given concurrently during the first and fifth weeks of radiation.Twenty-four among 31 eligible patients achieved complete response(77.4%) and the other seven (22.6%) partial response, resultingin a 100% response rate. The toxicities experienced were increasedcompared with those caused by radiotherapy alone. The most commonside effects were gastrointestinal and hematologic toxicitiesbut the whole treatment was well tolerated. The two-year actuarialsurvival rate is 45%. We found the primary origin and overalltreatment time to affect survival significantly. The survivalrate for tumors arising from the nasopharynx or paranasal sinusis better than for those arising from other regions of the headand neck. The shorter treatment times (within eight weeks) hada better survival rate. Our preliminary experience suggeststhat concomitant chemoradiotherapy is both feasible and effectivefor head and neck cancer. The optimal scheduling and dosageof concomitant chemoradiotherapy should be further researched.     

Feasibility of Non-Cisplatin-Based Induction Chemotherapy and Concurrent Chemoradiotherapy in Advanced Head and Neck Cancer

The purpose of the present study was to determine the safety and efficacy of induction chemotherapy followed by concomitant chemoradiotherapy. Thirty-eight patients were randomised to receive induction chemotherapy, consisting of cyclophosphamide and methotrexate followed by concomitant 5-fluorouracil and irradiation (study group) or irradiation alone (control group). There were non-significant differences in the initial tumor clearance rates in the two groups. Median disease-free survival (in complete responders) was 17 months (6-60+) vs 11 months (5-60+) (p = 0.407) and overall survival 11 months (1-60+) vs 14 months (2-60+) (p = 0.428) in the study and control groups respectively. Acute morbidity and deaths during intervention were higher in the study group (p = 0.007). This study suggests that induction along with concomitant chemoradiotherapy is too toxic for routine use and also fails to provide a survival benefit.     

Immunotherapy for Head and Neck Squamous Cell Carcinoma

Purpose of Review

Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents.

Recent Findings

Agents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (ICR). The anti PD1 agent, nivolumab, was recently approved by the FDA as a standard of care regimen for patients with platinum refractory recurrent/metastatic (R/M) HNSCC. Molecular pathways leading to resistance are starting to be identified, and work is underway to understand the most optimal treatment regimen with incorporation of immunotherapy.

Summary

ICR has renewed interest in the immunology of cancer, but resistance is not uncommon, and thus understanding of these mechanisms will allow the clinician to appropriately select patients that will benefit from this therapy.

     

Feasibility and Efficacy of Inspiratory Muscle Training in Patients with Head and Neck Cancer receiving Concurrent Chemoradiotherapy

Objectives: Patients with head and neck cancer (HNC) undergoing concurrent chemoradiotherapy (CCRT) often experience pulmonary symptoms. This study evaluated if a 7-week inspiratory muscle training (IMT) program during CCRT is feasible, adherent, and safe in patients with HNC. This study also evaluated the effect of IMT on diaphragm thickness, mobility, and cardiorespiratory parameters in patients with HNC receiving CCRT. Methods: Ten participants with advanced stage HNC receiving CCRT were recruited for the study. Feasibility, adherence, and safety of the intervention were the primary outcomes. Changes in diaphragm thickness and mobility, maximal inspiratory pressure, maximal expiratory pressure, forced vital capacity, forced expiratory volume in first second and functional capacity using 6-MWT were measured at baseline and post 7 weeks of CCRT. IMT was performed at one session per day for 5 days a week for 7 weeks. Eight sets of two minutes of inspiratory manoeuvres with one minute rest period between them with intensity of 40% MIP were given. Results: Ten participants  were included in this study out of the 13 patients screened, indicating the feasibility to be 76.9%. Participants completed a total of 260 training sessions out of the 350 planned sessions denoting the adherence level as 74%. Diaphragm thickness and MEP remained significantly unchanged while significant decline was seen in diaphragm mobility, MIP,FVC, FEV1 and 6-MWD at the end of 7 weeks. No adverse events were reported following the intervention. Conclusion: Inspiratory muscle training did not show significant effect on the diaphragm thickness, mobility, and cardiorespiratory parameters; however, it was feasible, adherent, and safe in patients with HNC receiving CCRT.     

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacityfor self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells areconsidered the ‘‘drivers’’ of the tumorigenic process in some tumor types, and have been named cancer stemcells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to theacquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype thatmay contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamouscell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase(ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive frontswhere endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment hasbeen shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel targetof study given their slow growth and innate mechanisms conferring treatment resistance. Further understandingof their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomesin patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells,with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due totreatment failure.     

Weekly Cisplatin-Based Concurrent Chemoradiotherapy for Treatment of Locally Advanced Head and Neck Cancer: a Single Institution Study

Background: The organ preservation approach of choice for the treatment of locally advanced head and neckcancers is concurrent chemoradiation with three weekly high doses of cisplatin. Although this is an efficacioustreatment policy, it has high acute systemic and mucosal toxicities, which lead to frequent treatment breaksand increased overall treatment time. Hence, the current study was undertaken to evaluate the efficacy ofconcurrent chemoradiation using 40 mg/m2 weekly cisplatin. Materials and Methods: This is a single institutionalretrospective study including the data of 266 locally advanced head and neck cancer patients who were treatedwith concurrent chemoradiation using 40 mg/m2 weekly cisplatin from January 2012 to January 2014. A p-valueof < 0.05 was taken to be significant statistically for all purposes in the study. Results: The mean age of the studypatients was 48.8 years. Some 36.1% of the patients had oral cavity primary tumors. The mean overall treatmenttime was 57.2 days. With a mean follow up of 15.2 months for all study patients and 17.5 months for survivors,3 year local control, locoregional control and disease free survival were seen in 62.8%, 42.8% and 42.1% of thestudy patients. Primary tumor site, nodal stage of disease, AJCC stage of the disease and number of cycles ofweekly cisplatin demonstrated statistically significant correlations with 3 year local control, locoregional controland disease free survival. Conclusions: Concurrent chemoradiotherapy with moderate dose weekly cisplatin isan efficacious treatment regime for locally advanced head and neck cancers with tolerable toxicity which canbe used in developing countries with limited resources.     

Hypofractionated Accelerated Radiotherapy with Concurrent Carboplatin for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Aims

Hypofractionated accelerated radiotherapy with concurrent carboplatin utilises both advantages of altered fractionation and synchronous chemotherapy to maximise local control in locally advanced head and neck cancer. Such fractionation schedules are increasingly used in the intensity-modulated radiotherapy era and the aim of this study was to determine the outcome of hypofractionated accelerated radiotherapy with carboplatin.

Materials and methods

One hundred and fifty consecutive patients with squamous cell carcinoma of the larynx, oropharynx, oral cavity and hypopharynx (International Union Against Cancer [IUAC] stage II-IV) treated with 55 Gy in 20 fractions over 25 days with concurrent carboplatin were analysed. Outcome measures were 2 year overall survival, local control and disease-free survival.

Results

The median follow-up in surviving patients was 25 months. IUAC stages: II n = 15; III n = 42; IV n = 93. Two year overall survival for all patients was 74.9% (95% confidence interval 66.0-81.7%). Two year local control was 78.3% (95% confidence interval 69.6-84.8%). Two year disease-free survival was 67.2% (95% confidence interval 58.3-74.7%). There were 135 patients with stage III and IV disease. For these patients, the 2 year overall survival, local control and disease-free survival were 74.3% (95% confidence interval 64.7-81.6%), 79.1% (95% confidence interval 69.8-85.9%) and 67.6% (95% confidence interval 58.0-75.4%), respectively. Prolonged grade 3 and 4 mucositis seen at ≥4 weeks were present in 9 and 0.7%, respectively. Late feeding dysfunction (determined by dependence on a feeding tube at 1 year) was seen in 13% of the surviving patients at 1 year.

Conclusion

Hypofractionated accelerated radiotherapy with concurrent carboplatin achieves a high local control. This regimen should be considered for a radiotherapy dose-escalation study using intensity-modulated radiotherapy.     

Head and Neck Squamous Cell Cancer: Biology (II) and Translational Methods

The essential steps implicated in carcinogenesis are acquisition of autonomous proliferative signaling; inhibition of growth inhibitory signals; evasion of apoptosis; immortalization; angiogenesis; tissue invasion and metastasis. A considerable progress in understanding the process of carcinogenesis has further stimulated the high throughput translational methods and systems biology approach to revolutionize this field of cancer biology. The era of molecular targeted therapy has dawned and would soon replace the more ‘toxic’ classical ‘broad-spectrum’ cancer chemotherapy. This review summarises the steps of carcinogenesis and the concepts involved in translational methods, systems-biology and molecular targeted therapy.     

Preoperative Concurrent Chemoradiotherapy for Stage IIIA Non-Small Cell Lung Cancer

Thirty-one patients with stage IIIA non-small cell lung cancer (NSCLC) were treated with preoperative concurrent chemoradiotherapy (CCRT) followed by surgery. The treatment protocol could not be completed in eight patients. The acute hematologic toxicities of grade III or IV occurred in 48.4% (15/31) after the first chemotherapy cycle, and in 39.1% (9/23) after the second cycle. The most common non-hematologic toxicity was radiation esophagitis. Surgery was attempted in 23 patients and successful in 22 patients (resection rate = 71.0%). Pathologic complete response and down-staging were achieved in 13.6% (3/22) and 68.2% (15/22). The median survival period, 2-year overall survival, local control and disease-free survival rates of all 31 patients and of 22 patients who underwent surgery were 19 months, 37.2%, 49.1%, 35.5%, and 19 months, 43.2%, 51.8%, 25.6%, respectively. On the basis of our observations, preoperative CCRT followed by surgery for stage IIIA NSCLC has resulted in outcomes comparable with those in previous reports.     

Salvage Transoral Robotic Surgery for Recurrent or Residual Head and Neck Squamous Cell Carcinoma: A Single Institution Experience

Background: The present study was conducted to evaluate the technical feasibility, safety and adequacy of surgical margins with salvage transoral robotic surgery (TORS) for recurrent or residual head and neck squamous cell carcinoma patients. Materials and Methods: Thirty patients who underwent salvage TORS using the ‘DaVinci’ robot were enrolled in the study and data related to their surgical time, complications and functional outcome were recorded. Results: The feasibility of salvage TORS in our study was observed to be 100%. Positive margins were encountered in only 6.7% of patients. Mean blood loss was 23.3 ml with no patient requiring blood transfusion. Postoperative complications in the form of primary haemorrhage requiring active surgical intervention occurred in 13.3%. Oral feeding could be started as early as the 3rd postoperative day in a few patients, with nasogastric tubes being removed on the 12th postoperative day. Long term gastrostomy tube dependency was seen in 10% cases. Median survival of patients was 19 months. Conclusions: Salvage TORS is a safe, effective and feasible option in the management of treatment failure cases. It offers an alternative surgical approach with unexpected benefits in terms of tracheostomy tube use, Ryle’s tube and gastrostomy dependence.     

局部晚期非小细胞肺癌同步放化疗进展

同步放化疗是局部晚期非小细胞肺癌的标准治疗方案,疗效明显优于序贯放化疗。诱导化疗不能改善总生存及无进展生存时间。巩固化疗尚有争议。与靶向治疗联合初步结果鼓舞人心。该文主要对以上内容进行综述。     

外泌体在头颈部鳞癌中的研究进展

摘 要：外泌体是一种携带多种生物活性物质的膜性囊泡,在介导肿瘤细胞—肿瘤细胞及肿瘤细胞—肿瘤微环境之间信息传递过程扮演重要角色。外泌体通过多种途径参与肿瘤发生发展,其在临床诊断和治疗方面也具有重要研究价值。全文对外泌体与头颈部鳞癌恶性进展、肿瘤微环境、耐药的关系及其在头颈部鳞癌诊断与治疗中的研究进展进行综述,以期为寻找头颈部鳞癌诊治新靶点提供线索。     

Weekly Cisplatin versus Standard Three-weekly Cisplatin in Concurrent Chemoradiotherapy of Head and Neck Cancer: the Baskent University Experience

Background: The majority of patients with head and neck cancer are treated with concurrentchemoradiotherapy. However, toxicity is substantial so that alternate schedules of cisplatin have been tried toovercome this problem. No formal comparison, however, has been reported between alternate schedules andreference regimen. Patients and methods: Fifty-five eligible patients treated with concurrent chemoradiotherapywere retrospectively analyzed. The patients treated with weekly cisplatin were defined as group A, while thepatients treated with standard regimen were defined as group B. Basic demographics and clinical characteristics’,overall survival rate, locoregional or systemic relapse rates, and time to local/systemic relapse were recorded.Results: One, two, and three-year probability of survival in groups A and B were 75% to 65% after one year,63% to 56%after two, and 63% to 52% after three, respectively. Although time to local and systemic relapse washigher in group B as compared to group A, a statistical analysis was failed to show any significant difference.Furthermore, there was no significant difference between groups with respect to major toxicity. Conclusion: Inpatients with head and neck cancer, concurrent chemoradiotherapy with weekly cisplatin might be as effectiveas concurrent chemoradiotherapy with bolus cisplatin.