Cisplatin-containing chemotherapy in advanced head and neck cancer

Sixty-two patients with previously untreated advanced head and neck cancer were admitted to a study of pre-radiotherapy combination chemotherapy containing cisplatin. After two courses only 3% were in complete response but 47% had achieved a partial response. Ninety per cent of patients completed radical radiotherapy and at least one course of chemotherapy; 54% of these achieved a complete response at 1 month post-therapy. The overall actuarial survival rate at 2 years was 40.3%, with a median survival of 12 months. The median survival of those with complete response 1 month after therapy has not yet been reached. The toxicity of the chemotherapy was low and no increase in morbidity from the subsequent radiotherapy was noted. Comparison with historical data from this hospital does not suggest any improvement in overall survival for the use of cisplatin-containing chemotherapy prior to radiotherapy.     

Locally advanced nasopharyngeal cancer: long-term outcomes of radiation therapy

PURPOSE: To investigate the clinical manifestations and treatment outcomes in patients with stage T4M0 nasopharyngeal carcinoma. MATERIALS AND METHODS: Findings in 179 patients (age range, 13-78 years) with American Joint Committee on Cancer stage T4M0 nasopharyngeal carcinoma treated from January 1983 to February 1992 with a minimum follow-up of at least 5 years were reviewed. Of the 179 patients, 166 (92.7%) had World Health Organization type II or III disease. Forty-one patients (22.9%) had no lymph nodal involvement; 138 patients (77.1%) had metastatic nodal involvement in the neck. All patients underwent radiation therapy; 39 patients also received different forms of chemotherapy. The radiation therapy doses were usually 70-74 Gy administered to the primary tumor over 7 or 8 weeks, 70-74 Gy to the neck region in patients with nodal involvement, or 50-60 Gy administered to the neck region over 5 or 6 weeks in patients without neck nodal involvement. RESULTS: In 100 patients, radiation therapy failed in the primary tumor alone (n = 28), neck nodes alone (n = 5), and distant metastases alone (n = 43) or at a combination of sites (n = 24). The cumulative failure rates for the primary tumor, neck metastases, and distant metastases were 25.1% (n = 45), 14.0% (n = 25), and 33.0% (n = 59), respectively. The 5-year primary disease-free, distant disease-free, and overall survival rates were 68.7%, 56.5%, and 28.6%, respectively. Results of salvage treatment for relapse were unsatisfactory. CONCLUSION: In about three-tenths of patients, T4M0 nasopharyngeal carcinoma can be cured with conventional high-dose radiation therapy.     

Sequential chemotherapy and radiotherapy in advanced head and neck cancer

Eighty-six previously untreated patients with advanced squamous-cell carcinoma of the head and neck were entered into a prospective randomised controlled trial to evaluate whether the addition of a kinetically based chemotherapy regimen before and after radiotherapy would improve survival compared with radiotherapy alone. Survival at 30 months showed there was no evidence that the addition of chemotherapy to radiotherapy improved survival and that the chance of obtaining a significant result in favour of adjuvant chemotherapy was remote. We make a strong plea that all chemotherapy regimens for the treatment of squamous-cell carcinoma of the head and neck regions should be subjected to controlled prospective trials before they are widely adopted.     

Complications associated with selective high-dose intraarterial cisplatin and concomitant radiation therapy for advanced head and neck cancer

PURPOSE: To describe the incidence and severity of complications associated with intraarterial cisplatin and concomitant radiation therapy for advanced head and neck cancer. MATERIALS AND METHODS: One hundred five patients treated between June 1993 and March 1998 were studied. Forty-seven (44%) had T4 lesions and 40 (37%) had bulky (N2/3) nodal disease. Three hundred eighty-five procedures were performed. All patients were treated with selective intraarterial tumor-directed cisplatin (150 mg/m(2) weekly x 4), simultaneous intravenous thiosulfate (9 g/m(2)) for systemic neutralization of cisplatin, and conventional external-beam radiation to the primary tumor and nodal disease (total dose of 66-74 Gy). RESULTS: One hundred five patients were evaluated for complications. Twenty-two (5.7%) groin hematomas occurred, none of which needed therapy. Two asymptomatic common carotid artery dissections were reported. Two patients experienced acute occlusion of the external iliac artery requiring a femorofemoral bypass. Overall, there were 41 grade III/IV chemotoxic events related to treatment. Chemotoxic events included 29 mucosal events, nine hematologic events, two otologic events, and one gastrointestinal event. No renal events occurred. There were three permanent and three transient neurologic events. CONCLUSION: Selective high-dose intraarterial cisplatin and concomitant radiation therapy for advanced head and neck cancer can be performed safely with a relatively low complication rate compared to standard intravenous chemotherapy treatment protocols.     

Intensity-modulated proton therapy (IMPT) versus intensity-modulated radiation therapy (IMRT) for the treatment of head and neck cancer: A dosimetric comparison

It is the goal of this study to compare the dosimetric advantages of IMPT when compared to IMRT. From January 2019 to August 2020, 25 patients were treated with intensity modulated proton therapy (IMPT) at our institution for either recurrent, metastatic, benign, or primary tumors in the head and neck region. Twenty-one patients met criteria for dosimetric analysis. Histology of disease included squamous cell carcinoma, acinic cell carcinoma, sarcomatoid sinonasal carcinoma, paraganglioma, adenoid cystic carcinoma, salivary high grade carcinoma, and papillary thyroid carcinoma. For IMRT planning, gross tumor volume (GTV) and clinical target volume (CTV) were contoured with the expansion of 3-5 mm to create the planning target volume (PTV) and dose was prescribed to the PTV. For the IMPT planning, dose was prescribed to CTV and robust optimization was utilized which accounted for a 5 mm setup and range uncertainty. The minimum, mean and maximum target doses for IMRT and IMPT plans as well as mean and maximum normal tissue doses are reported for the 21 patients meeting criteria. Mean doses for IMRT and IMPT were 6278.2 cGy and 6449.8 cGyRBE respectively with p-value of 0.0001. Maximum doses for IMRT and IMPT were 6579.5 cGy and 6772.1 cGyRBE respectively with p-value of 0.0014. Minimum doses for IMRT and IMPT were 5440.6 cGy and 5617.9 cGyRBE respectively with p-value of 0.3576. IMPT had an overall advantage in OAR doses in the brain stem, spinal cord, optic structures, cochlea, larynx, contralateral parotid, and oral cavity with only a few exceptions. Our study thus demonstrates a dosimetric advantage for IMPT in treating head and neck tumors in mean and max dose delivered as well as dose to OARs. Given that our patient cohort were mainly unilateral head and neck cases, our study supports the treatment of this specific subset of patients regardless of histology with IMPT. This may aid in appropriate patient selection for IMPT treatment. Further studies will need to determine if this dosimetric advantage translates to a therapeutic advantage for patients.     

Serial FDG-PET on patients with head and neck cancer: Implications for radiation therapy

Purpose: To assess possible consequences for radiotherapy (RT) planning, e.g., reduction of treatment volume by a decreased tumour volume in Fluor-18-fluoro-deoxy-glucose-Positron emission tomography (FDG-PET) based on a close-meshed evaluation of FDG uptake in primary head and neck cancer (HNC) during RT.

Materials and method: PET data were analysed using a source-to-background based algorithm. The following parameters were obtained: max. standardised uptake value (SUVmax), PET-based gross tumour volume (GTV-PET) and metabolic volume (MV).

Results: While the median SUVmax decreased (initial: 15.2, 1st/2nd week: 10.2, 3rd/4th week: 6.5, 5th/6th week: 6.4), the median values of GTV-PET (9.3 cm³, 12.4 cm³, 14.0 cm³, 17.9 cm³) and MV (92.2 cm³, 61.7 cm³, 60.0 cm³, 71.3 cm³) seemed to increase during radiotherapy. The intra-individual development of SUVmax could be divided into two groups: group A having continuously decreasing values of SUVmax (n = 10 patients), and group B having a temporary increase of SUVmax (n = 13).

Conclusions: Data suggest that a reduction of treatment volume is not possible by an adaptive re-planning based on FDG-PET, e.g., at 50 Gy. This may be caused by a consecutive therapy associated inflammation. This limitation is probably related to the use of a source-to-background based algorithm.     

Results of fast neutron therapy in advanced head and neck cancer

Eighty-nine patients with advanced head and neck cancer were treated with a fast neutron beam of mean energy 5.6 MeV. The standard tumour dose was 1320 cGyn, gamma in 20 fractions over 4 weeks, but 13 patients with laryngeal cancer received 1200 cGyn, gamma. Complete remission was achieved in 50 patients (56%). Fifteen patients (17%) survived 2 years, 14 of them being symptom-free. Survival correlated with the stage of disease. Encouraging results were obtained for cervical node metastases, oropharynx and salivary gland cancer. In laryngeal and hypopharyngeal cancer, neutron therapy seems to be disadvantageous. The main reason for treatment failure was local recurrence. Two patients died of complications.     

Risk factors for local-regional recurrence following preoperative radiation therapy and surgery for head and neck cancer (stage II-IVB)

PURPOSE: To discover possible risk factors for local-regional recurrence (LRR) following preoperative radiation therapy and curative surgery for head and neck squamous cell carcinoma (SCC) (stage II-IVB). MATERIALS AND METHODS: Clinical records from 1987 to 1999 of 161 patients with head and neck SCC (oral cavity, 80 patients; larynx, 50; hypopharynx, 19; oropharynx, 12) who underwent preoperative radiation therapy and surgery were retrospectively reviewed. One hundred thirty-two (82%) of the patients had stage III or IV cancer. The median radiation dose was 38 Gy. RESULTS: The 5-year overall survival rate and LRR rate were 58% and 35%, respectively. At multivariate analysis, oral cavity cancer (P =.020), clinical T stage (P =.016), clinical N stage (P =.017), and status of surgical margins (P =.008) emerged as variables that were significantly associated with LRR. The analysis of only those patients with lymph node involvement showed that oral cavity cancer (P =.008), advanced N-stage cancer (P =.045), and long interval between the start of preoperative radiation therapy and surgery (> or =7 weeks) (P =.019) emerged as variables that were significantly associated with LRR. CONCLUSION: Oral cavity cancer, advanced T or N stage of disease, and unsatisfactory margins were risk factors for LRR. A long interval (> or =7 weeks) was a risk factor for LRR in patients with lymph node involvement.     

Radiation therapy for head and neck cancer

Radiation therapy is the first choice of treatment for most of the early squamous cell carcinoma of the head and neck. Conventional radiotherapy however, contributes to the high local control rates only for carcinoma of the glottic larynx and the nasopharynx. Squamous cell carcinoma of the other sites cannot be sterilized easily only by external beam radiation therapy alone. Chemoradiotherapy, conformal three-dimensional radiotherapy and multi-daily fractionation are introduced clinically to improve local control and/or survival for radioresistant tumor. In this review, consensus report of radiation therapy for carcinoma of the larynx and pharynx, which was reached an agreement in JASTRO meeting in 1998, is introduced. The role of radiation therapy in the management of head and neck cancer in present and near future is also discussed.     

Complications of combined surgery and neutron radiation therapy in patients with advanced carcinoma of the head and neck.

A total of 135 patients with advanced squamous-cell carcinoma of the head and neck were treated with cyclotron-generated fast neutrons. Thirty-eight had major surgery before or after irradiation. Major complications (fistula formation, carotid artery exposure or blowout requiring ligation, or major wound breakdown) occurred in 37%. The complication rates associated with surgery prior to irradiation, planned surgery following irradiation, and salvage surgery following irradiation were 0/12, 4/5, and 10/21, respectively. The complication rate for surgery following neutron irradiation alone was 73%; for surgery following mixed-beam irradiation it was 20%. The age of the patient and the interval between surgery and irradiation had no influence on the complication rate.     

Induction chemotherapy followed by simultaneous hyperfractionated radiochemotherapy in advanced head and neck cancer

Purpose

To evaluate the feasibility of induction chemotherapy followed by concomitant chemotherapy and hyperfractionated irradiation in locally advanced, inoperable head and neck cancer.

Methods

A pilot study was undertaken comprising 3 cycles of cisplatinum (100 mg/m², day 1) and 5-fluorouracil (1000 mg/m² in continuous intravenous infusion over the first 120 h) followed by bifractionated radiotherapy applied to tumor/involved lymph nodes up to the dose of 74.4 Gy given in 2 fractions of 1.2 Gy daily for 5 days a week combined with concomitant weekly cisplatinum infusion (50 mg/m²).

Results

Six patients were enrolled in the study. All of them completed the protocol therapy. Severe mucositis and myelotoxicity were the most common acute side effects observed in all and in 5 of the patients, respectively. Acute toxicity required interruption of concomitant chemotherapy in 5 cases and in 2 interruption of radiotherapy was necessary. Opioid analgesic parenteral therapy was administered in 4 patients. Three of them had to be hospitalized. One patient experienced cerebral stroke 1 day after the completion of therapy and died 7 days later. Due to high acute toxicity, patient accrual was terminated after 6 patients. At the mean follow-up of 17 months, 4 patients are alive, 3 of them are free of disease and in 1 local progression has been diagnosed.

Conclusions

High acute toxicity of induction cisplatinum and 5-fluorouracil followed by concomitant cisplatinum and hyperfractionated irradiation calls for less toxic treatment schedules in locally advanced inoperable head and neck cancer.     

Recurrent head and neck cancer: retreatment of previously irradiated areas with combined chemotherapy and radiation therapy-results of a prospective study

PURPOSE: To prospectively test the effectiveness of combined chemotherapy and radiation therapy for recurrent head and neck cancer. MATERIALS AND METHODS: In 32 patients, external-beam radiation therapy (2 Gy/d) was administered as a 5-day course with simultaneous hydroxyurea (1.5 g/d orally) and 5-fluorouracil (300 mg/m(2)/d bolus), followed by 9 days of rest. This cycle was repeated until a cumulative soft-tissue radiation dose of 110 Gy (including prior radiation therapy) was reached. RESULTS: At a median follow-up of 18 months, three patients were alive, and 29 had died. The overall 1-year survival rate was 39%. The overall response rate was 41% (13 patients). Acute toxicity was low. According to World Health Organization and Radiation Therapy Oncology Group criteria, there were three cases of grade 3 mucositis or dermatitis and three cases of grade 3 or 4 neutropenia. Three patients had grade 3 late effects: one oral trismus, one jugular venous thrombosis, and one cerebral stroke. CONCLUSION: The combination of simultaneous 5-fluorouracil and hydroxyurea infusion and local reirradiation is feasible for retreatment of recurrent head and neck tumors. This regimen provides short-term tumor control in most patients and long-term control in a few patients.     

BNCT for advanced or recurrent head and neck cancer

The therapeutic effect of surgery and/or combination of conventional chemoradiotherapy is limited in the patients with recurrent squamous cell carcinoma (SCC) and locally advanced non-squamous cell carcinoma without malignant melanoma (non-SCC) of the head and neck. Currently, clinical trials of BNCT for head and neck cancers are being conducted in some institutes to verify its the effectiveness. BNCT was performed in 10 patients with recurrent SCC, 7 patients with recurrent non-SCC and 3 patients with newly diagnosed non-SCC in our university between October 2003 and September 2007. Eleven patients showed complete remission and 7 patients showed partial remission of irradiated site. The effective rate [(CR+PR)/total cases] was 90%. No severe acute or chronic normal-tissue reactions were observed in any patients. BNCT is effective and safe in the patients with recurrent SCC and locally advanced non-SCC.     

Neurological changes following radiation therapy for head and neck tumours

Radiation therapy is widely used in the treatment of head and neck tumours either as a primary form of treatment or a supplementary modality. Although the benefits of radiation therapy are well established, this treatment modality is not without untoward consequences and complications. The intent of this paper is to highlight the neurological complications that may follow the treatment for head and neck malignancies, in particular, following radiation therapy for nasopharyngeal carcinoma.