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.     

Cisplatin as Second Line Chemotherapy in Advanced or Recurrent Squamous Cell Carcinoma of Head and Neck Region

Thirty-two patients with advanced or recurrent carcinoma of the head and neck were treated with cis-dichlorodiaminoplatinum II (CDDP) 75 mg/m² every third week as second line chemotherapy. The response rate was 3 per cent with one complete and no partial responders, 16 patients with no change and 10 with progressive disease. Five were not evaluated concerning response. Median time to progression was 12 weeks (confidence limits 10--17 weeks) and median survival time 21 weeks (confidence limits 10 to 33 weeks, range 4 to 109). No severe hematologic toxicity was seen. Two patients had progressive polyneuropathy, one had a severe decline in Cr-EDTA-clearance and in one decline in auditory function was suspected. It is concluded that CDDP in this schedule has no role as second line chemotherapy in advanced cancer of head and neck.     

Induction Chemotherapy (Cisplatin + 5-Fluorouracil) and Radiotherapy in Advanced Squamous Cell Carcinoma of the Head and Neck

A phase 11 study was made of 58 consecutive patients with previously untreated locally advanced squamous cell carcinomas of the head and neck. The induction chemotherapy consisted of 3 courses of cisplatin (100mg/m²) and a subsequent 120-h infusion of 5-fluorouracil (1 000 mg/m²/24 h) repeated every 3 weeks. It was followed by radiotherapy to a median target dose of 66 Gy and surgery for residual tumour. A total of 91 per cent received all 3 courses of chemotherapy, which was well tolerated. Complete response (CR) was obtained in 20 patients (35%) after chemotherapy and in 40 patients (69%) after subsequent radiotherapy. The median observation time was 28 months (range 15-57). The actuarial survival at 2 years for complete responders to chemotherapy was 83 per cent, implying a prolonged survival (p = 0.002) compared to those with less than CR. Complete responders after chemotherapy had also a significantly longer recurrence-free survival, though 19 out of 20 did not undergo surgery. Complete response after this induction therapy is thus an important prognostic predictor.     

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.

     

Response Rate of Cisplatin Plus Docetaxel as Primary Treatment in Locally Advanced Head and Neck Carcinoma (Squamous Cell Types)

Objective: To evaluate the response rate of Cisplatin plus Docetaxel in the treatment of locally advanced head and neck squamous cell carcinomas (HNSCC) at a tertiary care hospital in Karachi, Pakistan. Materials and Methods: It was a longitudinal study, conducted at the Department of Medical Oncology, Jinnah Postgraduate Medical Center, Karachi, Pakistan from December 2018 to June 2019. One hundred patients of age 14-66 years of age of either gender with histologically proven Squamous Cell Carcinoma of Head and Neck, Stage III and IV (locally advanced) with no distant metastases were included in the study. Patients who were declared unresectable by the otolaryngologist and those with delayed appointment for radiation were given 3 cycles of Induction Chemotherapy with Cisplatin and Docetaxel, both at a dose of 75mg/m2 3 weekly. After 3 cycles, CT scan was repeated to assess the clinical response. Those patients who had partial or complete response as per RECIST criteria were re-assessed by the otolaryngologist and were planned for surgery if disease became resectable while other patients were referred for Concurrent Chemo-Radiation Therapy (CCRT). SPSS version 23 was used to analyze data. Results: The partial response was achieved in majority of the patients after Induction Chemotherapy with Docetaxel and Cisplatin (62%) with a complete response in 12 %. However, 22% showed progression of the disease, and 4% showed stable disease. The most frequent side effects observed were diarrhea (62%) and neutropenia (57%). Conclusion: Induction chemotherapy with Cisplatin and Docetaxel is a promising regimen with good response and favorable toxicity profile and can be considered as a potentially effective outpatient regimen for locally advanced squamous cell carcinoma of head and neck.     

Molecular Targets in Squamous Cell Carcinoma of the Head and Neck

Opinion statement Worldwide more than a half million people develop Head and Neck cancer annually. Despite a significant decrease in smoking, about 40,000 new patients are diagnosed with carcinoma of the head and neck annually in the United States, and 11,000 of them succumb to their disease. More than 90% of these cancers are squamous cell carcinoma. The survival rates of patients with squamous cell carcinoma of the head and neck (SCCHN) have not improved significantly despite multimodality therapy including surgery, radiation therapy, and chemotherapy. Recently, molecular targeted agents have shown significant improvement in clinical outcomes in chronic myelogeneous leukemia with imatinib, breast cancer with trastuzumab, colon cancer with bevacizumab and cetuximab, and renal cell cancer with sorafenib and sunitinib. In SCCHN the epidermal growth factor receptor (EGFR) antibody cetuximab has shown promising results in a phase III trial in combination with radiation. How best to integrate these agents with the traditional treatment modalities of surgery, radiotherapy, and cytotoxic chemotherapy is of vital importance but has yet to be determined. This article will discuss the biology of molecular targeted agents as well as current clinical trials and future directions of these agents in SCCHN.     

Radiochemotherapy in Locally Advanced Squamous Cell Carcinomas of the Head and Neck

Squamous cell carcinoma of the head and neck (SCCHN) is a common disease that develops in the upper aerodigestive epithelium. The most important risk factors are tobacco and alcohol consumption. There is also increasing evidence that human papillomavirus plays an important role in the cause of SCCHN. The complex anatomy, the vital functions of the upper aerodigestive tract and the close proximity to vital structures, explain that the goal of treatment is not only to improve survival outcomes, but also to preserve organ function. Radiotherapy and surgery are the standard modalities of treatment, reflecting the locoregional predominance of SCCHN. Chemotherapy plays an important role in the treatment of patients with locoregionally advanced disease, in conjunction with radiotherapy and surgery. Indeed, standard therapy for resectable locoregionally advanced (stage III or IV) SCCHN cancers consists either of surgery and adjuvant chemoradiotherapy or definitive concomitant chemoradiotherapy, depending upon disease site, stage and resectability of the tumour, or institutional experience. Concomitant chemoradiotherapy has been shown in several randomised trials to improve disease-free and overall survival in the postoperative setting for resected disease with poor prognostic factors. Furthermore, multiple randomised studies and meta-analyses have shown that definitive chemoradiotherapy, as well anti-epidermal growth factor receptor treatment in one randomised study, improved disease-free and overall survival when compared with radiotherapy alone. This overview reviews the most relevant published studies on the multidisciplinary management of SCCHN and discusses future strategies to reduce locoregional failures.     

Chemo-Radiotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Factors Affecting Toxicity Patterns

Abstract

Radiation and chemotherapy in the treatment of locally advanced squamous carcinoma of the head and neck can be used according to different strategies: concomitant, alternation, consecutive. The limiting acute toxicity is local with the radiosensitizing capacity of the drug and type of radiation fractionation being the predominant factors. Regimens providing more that 50% of complete responses are usually associate with a more than 40% incidence of severe local reaction. More information is needed on late toxicity that influences the quality of life for these patients.     

铁死亡在头颈部鳞状细胞癌中的研究进展

头颈部鳞状细胞癌(HNSCC)作为全球发病率极高的癌症之一,由于晚期HNSCC手术治疗后易发生术后复发及对部分化疗药物的耐药性,患者预后情况并不乐观.因此,提高化学药物治疗HNSCC的效率,改善HNSCC患者预后成为目前亟需解决的问题.最新研究发现铁死亡对部分类型的肿瘤细胞的生长增殖具有调节作用,一定程度上降低了肿瘤治...     

Simultaneous Radiotherapy and Chemotherapy with Carboplatin in Inoperable Squamous Cell Carcinoma of the Head and Neck: A Phase II Study

Fifty-six untreated patients with inoperable squamous cell carcinoma of the head and neck were treated with carboplatin 70 mglm² i.v. daily on days 1-5 and 29-33 in combination with simultaneous conventional radiation up to a target volume dose of 50 Gy. Depending on tumor response and upon recommendation of surgeons, 21 of 56 patients underwent surgery after a radiation dose of 50 Gy and two courses of carboplatin. Patients who showed pCR after surgery received no further radiotherapy. In all other patients radiotherapy was continued using a shrinking field technique up to a target absorbed dose of 70-74 Gy. Combined modality induced 66% complete remission (CR) and an overall response rate of 98%. After completion of the whole treatment program (combined modality ± surgery) 53 (94%) of the 56 patients were disease free. The median survival for all patients is 25+ months and the percentage of two-year survivors is 53%. Myelosuppression was the most frequent toxicity, but rarely was severe; leukopenia and thrombocytopenia of WHO grade 3 occurred in 21% of the patients. No other toxicities above WHO grade 2 occurred. Nephrotoxicity, neurotoxicity and ototoxicity were not seen. The addition of carboplatin did not increase the rate of surgical complication over that expected for preoperative radiotherapy. Two patients died of pulmonary embolism after surgery. Combined modality with carboplatin and simultaneous radiation is a highly active and well-tolerated regimen for untreated patients with inoperable squamous cell carcinoma of the head and neck.