Claes Mercke

Malnutrition and food intake in relation to quality of life in head and neck cancer patients

The quality of life (QL) of cancer patients has attracted an increasing interest in recent years. Patients with head and neck cancer often have troublesome symptoms due to the disease and to treatment side effects, which will have an impact on the patients QL. The aim of this study was to evaluate the possibility of studying QL in relation to well‐known clinical parameters.

Tumor radiosensitivity (SF2) is a prognostic factor for local control in head and neck cancers.

PURPOSE To evaluate prospectively the prognostic value of SF2 for local control and survival in patients undergoing radiation therapy for head and neck cancers. METHODS AND MATERIALS Following informed consent tumor specimens were obtained from 156 patients with primary carcinomas of the head and neck region. The specimens were assessed for the ability to grow in vitro (colony forming efficiency, CFE) and inherent radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft-agar clonogenic assay. Patients were treated mainly with neoadjuvant chemotherapy plus radiation therapy usually as a combination of accelerated external beam and interstitial radiotherapy. The probabilities of local control and survival were analyzed by univariate, bivariate and Cox multivariate analyses. RESULTS Successful growth was achieved in 110/156 specimens and SF2 values were obtained from 99/156. Eighty four out of these patients underwent radical treatment. The median SF2 value for the 84 tumors was 0.40. At a mean follow-up time of 25 months (range 7-65) the median SF2 value of tumors from 14 patients who developed local recurrence was 0.53, which was significantly higher than the median of 0.38 for tumors from 70 patients without local recurrence (p = 0.015). Tumor SF2 was a significant prognostic factor for local control (p = 0.036), but not for overall survival (p = 0.20). Tumor SF2 was an independent prognostic factor for local control within bivariate and Cox multivariate analyses. CONCLUSIONS This study has shown that tumor radiosensitivity measured as SF2 is a significant prognostic factor for local control in head and neck cancers.

Combined treatment with temporary short-term high dose rate Iridium-192 brachytherapy and external beam radiotherapy for irradiation of localized prostatic carcinoma

PURPOSE To evaluate the treatment outcome after radical radiotherapy of localized prostate cancer in 50 patients (38 patients with stage T1-2 and 12 patients with stage T3) after a median follow-up time of 45 months (range 18-92 months). METHODS The treatment was given by combination of external beam radiotherapy (50 Gy) and brachytherapy (2 x 10 Gy). The brachytherapy was given using TRUS-guided percutaneously inserted temporary needles with a high dose rate remote afterloading technique with Ir-192 as the radionuclide source. Three target definitions and dose levels inside the prostate gland were used. Local control was evaluated by digital rectal examination, TRUS-guided biopsies and serum PSA evaluations. RESULTS Clinical and biopsy verified local control was achieved in 48 of the 50 (96%) patients; for stage T1-2 in 37 of 38 (97%) patients and for stage T3 in 11 of 12 (92%) patients. A posttreatment serum PSA level < or =1.0 ng/ml was seen in 42 (84%) patients, values from >1.0 to < or =2.0 ng/ml were seen in four (8%) patients and values exceeding 2.0 were seen in four (8%) patients. The late toxicity was minimal. CONCLUSION The local control results and the minimal toxicity after the combined radiotherapy treatment are promising. However, long term results are necessary before general use.

A prospective quality of life study of patients with oral or pharyngeal carcinoma treated with external beam irradiation with or without brachytherapy

The aim of this longitudinal quality of life (QL) study, was to study tumour-related symptoms and treatment side-effects of patients with oral or oropharyngeal cancer and to determine whether an increased local dose of irradiation (brachytherapy affected QL. The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), a tumour-specific Head and Neck questionnaire and the Hospital Anxiety and Depression scale (HAD) were used repeatedly during 1 year. There were 105 patients, with a cumulative response rate of 89%. Most symptoms and problems were at their peak 2 or 3 months after the start of treatment. Nutrition and pain were found to be the major problems, and as many as 19-40% reported psychiatric distress. Patients having received additional brachytherapy did not report any increase in QL problems (except for pain) compared with those having had external radiation only. Quality of life does not seem to be affected by the increased irradiation local dose given when brachytherapy is included in the treatment regimen.

IRRADIATION OF LOCALIZED PROSTATIC CARCINOMA WITH A COMBINATION OF HIGH DOSE RATE IRIDIUM-192 BRACHYTHERAPY AND EXTERNAL BEAM RADIOTHERAPY WITH THREE TARGET DEFINITIONS AND DOSE LEVELS INSIDE THE PROSTATE GLAND

PURPOSE Localized prostate cancer was treated with combined external beam radiotherapy and high dose rate Ir-192 brachytherapy with the purpose of a high dose. The technical aspects of a modified treatment are described. METHODS The brachytherapy was given in two sessions preceded and succeeded by external beam radiation. The radioactive source was temporarily implanted by a remote afterloading device through six to 15 needles inserted transperineally guided by transrectal ultrasound. The entire prostate gland was included in the clinical target volume. The urethra and the tumour volume could be defined and irradiated to different dose levels in more than 90% of the patients. RESULTS Fifty-four patients were treated. The total dose to the prostate was approximately 70 Gy and to the tumour volume 80 Gy. By calculating the corresponding dose given by 2.0 Gy fractions, considering the radiobiology by using the LQ formula and assuming an alpha/beta value for prostate tissue of 10, the dose to the prostate was approximately 84 Gy and to the tumour volume 112 Gy. For the late effects to the urethra an alpha/beta value of 3 was used, which corresponds to 85 Gy. The brachytherapy could be given with accuracy except when the dorsal border of the prostate was concave. The dose distribution then tended to be less satisfactory. Post-treatment calculations showed that the maximum dose to the rectum was 67 Gy (radiobiologically corrected to 88 Gy), given in a small volume. The early side effects from the brachytherapy were minimal. The treatment could not be performed as intended in four patients; three patients had a narrow pelvis and in one patient the prostate was unusually resilient, preventing the needles from being positioned properly. CONCLUSIONS This modification of a previously reported brachytherapy technique for prostate carcinoma permits a high radiation dose to the tumour and to the prostate gland, which ultimately may improve local control.

Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil

Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.

Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the head and neck: a randomized Phase III study

BACKGROUND AND PURPOSE In 1986 a prospective, randomized, multi-centre trial for evaluation of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in the treatment of advanced squamous cell carcinoma of the head and neck was initiated. As survival in this group of patients is poor the purpose was to find a possible survival benefit of the chemotherapy in addition to radiotherapy compared to radiotherapy only. METHODS Four-hundred sixty-one patients from Denmark, Norway and Sweden with tumors in oral cavity, oropharynx, hypopharynx and larynx were randomized to receive either standard treatment (radiotherapy or radiotherapy followed by surgery) or neoadjuvant chemotherapy followed by standard treatment. Chemotherapy included three courses of cisplatin 100 mg/m2 i.v. infusion on day 1 followed by 5-fluorouracil 1000 mg/m2 per day continuous i.v. infusion for 120 hours. Radiotherapy 64-70 Gy in 2 Gy per fraction, 5 times/week, was given to patients in both treatment arms. RESULTS Response rate was 71% for patients randomized to chemotherapy-radiotherapy and 66% for patients randomized to standard treatment (not statistically significant). Residual tumors were excised if possible. After surgery 62% of the patients randomized to chemotherapy-radiotherapy and 60% of the patients in the standard treatment group were clinically tumor free. CONCLUSIONS No statistically significant benefit in survival was observed for patients treated with neoadjuvant chemotherapy followed by radiotherapy. Nor was there any impact of chemotherapy on the number of patients achieving loco-regional tumor control after primary treatment.

Systematic set-up errors for IMRT in the head and neck region: effect on dose distribution

BACKGROUND AND PURPOSE There is a general concern about intensity modulated radiation therapy (IMRT) treatments being more sensitive to patient positioning than conventional treatments. The aim of this study was to evaluate the International Commission on radiation units and measurements (ICRU) method for taking systematic set-up errors into account for IMRT treatments and to compare the effects on the dose distribution with the effects of conventional treatments. MATERIAL AND METHODS A planning margin to account for set-up errors was added to the clinical target volumes and to the spinal cords, for three head and neck patients, according to the ICRU. No margin was added to organs at risk with mainly parallel structure if they were situated adjacent to the target volume, for example, the parotid glands. The effects of set-up errors in six IMRT plans and three conventional plans were simulated in the planning system and analysed with physical dose parameters. RESULTS AND CONCLUSIONS In general, the ICRU method of taking set-up errors into account works satisfactorily for IMRT treatments as well as for conventional treatments with no difference between the treatment techniques. The sensitivity to set-up errors regarding the target volume is dependent on the quality of the treatment plan, i.e. the part of the target covered with a dose >95 and <105% and the effect in the critical organs is dependent on the sharpness of the dose gradients outside the critical organ. However, the method makes it difficult to include organs at risk with mainly parallel structure if they are situated adjacent to the target volume.

Prognostic Factors for Local Control and Survival of Cancer of the Oral Tongue a retrospective analysis of 230 cases in Western Sweden

During the 19-year period from 1970 to 1988, 289 cases of squamous cell carcinoma of the oral tongue were diagnosed in Western Sweden. In 230 of these, treatment regimens and results were analysed in an attempt to define prognostic factors for local control and survival. Tumour stages were: T1 26%, T2 32%, T3 30% and T4 13%. Nodal disease was seen in 32% of the patients. Sixty per cent of the patients had surgery, 74% external with or without combination with interstitial irradiation; and 32% received chemotherapy. The local control rate at five years was 59% (T1 66%, T2 67%, T3 44% and T4 0%). Survival at five years was 37% (T1 61%, T2 51%, T3 19% and T4 0%). By a multivariate procedure we demonstrate that the tumour related variables T-category, N-category and extension to the tonsillar region had a significant association with survival. Extension to the tonsillar region, extension to the floor of the mouth and level of neck nodes were significantly associated with local-regional control.

Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma The ARTSCAN study

BACKGROUND AND PURPOSE Studies on accelerated fractionation (AF) in head and neck cancer have shown increased local control and survival compared with conventional fractionation (CF), while others have been non-conclusive. In 1998 a national Swedish group decided to perform a randomised controlled clinical study of AF. MATERIALS AND METHODS Patients with verified squamous cell carcinoma of the oral cavity, oropharynx, larynx (except glottic T1-T2, N0) and hypopharynx were included. Patients with prior chemotherapy or surgery were excluded. Patients were randomised to either CF (2Gy/day, 5days/week for 7 weeks, total dose 68Gy) or to AF (1.1Gy+2.0Gy/day, 5days/week for 4.5weeks, total dose 68Gy). An extensive quality assurance protocol was followed throughout the study. The primary end point was loco-regional tumour control (LRC) at two years after treatment. RESULTS The study was closed in 2006 when 750 patients had been randomised. Eighty-three percent of the patients had stages III-IV disease. Forty eight percent had oropharyngeal, 21% laryngeal, 17% hypopharyngeal and 14% oral cancers. There were no significant differences regarding overall survival (OS) or LRC between the two regimens. The OS at two years was 68% for AF and 67% for CF. The corresponding figures for LRC were 71% and 67%, respectively. There was a trend towards improved LRC for oral cancers treated (p=0.07) and for large tumours (T3-T4) (p=0.07) treated with AF. The AF group had significantly worse acute reactions, while there was no significant increase in late effects. CONCLUSION Overall the AF regimen did not prove to be more efficacious than CF. However, the trend towards improved results in AF for oral cancers needs to be further investigated.