Palliative interventions and prognosis in patients with advanced esophageal cancer.

In a retrospective review, in order to describe the palliative care and prognosis of patients with advanced cancer of the esophagus, the clinical characteristics and the treatment modalities applied were explored in relation to survival and symptom relief for 261 patients treated without curative potential. The data were obtained from a study of all patients with cancer of the esophagus treated at the Norwegian Radium Hospital in the 10-year period from 1990 to 1999. Medical data of the patients were reviewed and missing clinical information was retrieved from local hospitals and general practitioners. The patients were divided into three groups based upon the overall survival from start of treatment to death. Survival ≤3 months is in this paper, defined as 'short,' while survival > 6 months is defined as 'long.' Median survival for the total group of patients was 4 months. The 1-, 2-, and 3-year survival was 8%, 3%, and 1%, respectively. Patients with short survival (n= 107) had more advanced disease, lower performance status, and more dysphagia, weight loss, and pain and used more analgesics than patients with long survival (n= 91). Tumor characteristics such as localization, tumor length, and histology were not significantly associated with survival. This result was confirmed in a logistic regression analysis (with backward stepwise elimination) including sex, age, clinical stage, tumor length, tumor localization, histology, performance status, dysphagia, weight loss, and pain, where clinical stage, performance status, weight loss, and pain were included in the final model. A large variety of first-line palliative treatments were applied within the studied time period; external radiotherapy ± brachytherapy (n= 149), brachytherapy alone (n= 44), endoluminal stent (n= 28), laser evaporization (n= 8), chemotherapy (n= 5), and best supportive care only (n= 27). There were no clear differences in the effect on dysphagia between the modalities. Fourteen percent of the patients had treatment related complications. In conclusion, symptoms, performance status, and use of analgesics seemed to better prognosticate survival than tumor characteristics other than stage of disease. Our study reveals that knowledge about prognostic factors is crucial for the choice of palliative treatment. Even though all of the different treatment modalities seemed to provide relief of dysphagia, several other factors should be considered when deciding which treatment modality to offer. The time to onset of relief, duration of response, level of complications, and time spent in hospital should be a part of the decision-making process when selecting the appropriate treatment.

The value of follow-up in patients treated for squamous cell carcinoma of the head and neck.

Clinical findings, treatment and results have been recorded prospectively in 661 patients with carcinoma of the head and neck. With an average follow-up of 3 years 7813 follow-up consultations revealed 220 recurrences. The overall "recurrence pick-up rate" and subsequent "cure rate" was 1:36 and 1:113 consultations, respectively. Laryngeal carcinomas treated with radiotherapy and oral carcinomas receiving radiotherapy and limited resections showed recurrence "cure-rates" of 1:89 and 1:110, respectively. For other tumour sites the average "cure-rate" was 1:238. Only 39% of the recurrences were detected through physical examination. Follow-up consultations revealed 9.1% of second primaries. More time should be spent on training patients to recognise symptoms and signs of recurrence. Routine follow-up is rarely indicated beyond the third year after completion of treatment, or in patients for whom we have little to offer in terms of curative treatment.

Phase I/II study of carboplatin and 5-fluorouracil in patients with advanced head and neck carcinoma.

59 patients with histological verified squamous cell carcinoma of the head and neck, 39 with primary disease and 20 with relapse were given carboplatin and 5-fluorouracil (5-FU) in escalated carboplatin doses. The starting dose with carboplatin was 200 mg/m2 and the dose was escalated to 300 mg/m2, 350 mg/m2, 400 mg/m2 and thereafter by 20 mg/m2 per step. All patients received a dose of 1000 mg/m2 5-FU as a continuous infusion for 5 days. The myelotoxicity was moderate. No patients had grade 4 haemoglobin toxicity, while 7 patients had grade 3 toxicity. 2 patients had grade 4 leucocyte toxicity and 1 patient had grade 3. 4 patients were observed with a grade 4 platelet toxicity. 2 early deaths occurred at a dose level of 420 mg/m2. 18 out of 39 patients in primary treatment responded while 2 out of 20 patients treated for relapse responded. On the basis of the present study the maximum tolerable dose for carboplatin in combination with 5-FU 1000 mg/m2 is between 350 and 400 mg/m2.

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.

Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources.

The aim of this prospective randomized study was to compare the clinical and cosmetic outcome of superficial basal cell carcinomas (BCC), using either laser or broadband halogen light, in photodynamic therapy with topical 5-aminolevulinic acid (ALA). A total of 83 patients with 245 superficial BCC were included in the study. Standard treatment involved 15 min of local pretreatment with 99% dimethylsulfoxide (DMSO) before topical application of 20% ALA with DMSO (2%) and ethylendiaminetetraacetic acid (2%) as cofactors for 3 h before light exposure with either laser or a broadband lamp (BL). A complete response was achieved in 95 lesions (86%) in the laser group and 110 lesions (82%) in the BL group 6 months after treatment. Of these, 80 lesions (84%) in the laser group and 101 lesions (92%) in the lamp group were independently evaluated to have an excellent or good cosmetic post-treatment score. No serious adverse events were reported. This study shows that there is no statistical significant difference in cure the rate (P = 0.49) and the cosmetic outcome (P = 0.075) with topical application of a modified ALA-cream between light exposure from a simple BL with continuous spectrum (570-740 nm) or from a red-light laser (monochromatic 630 nm). Cost and safety are further elements in favor of the BL in this setting.

Fistulae following laryngectomy in patients treated with irradiation.

The development of fistulae following 197 consecutive laryngectomies performed from 1980 to 1987 have been examined. Fistulae were present in 28 patients (14 per cent). Age, T-classification, daily level of radiation dose and the time lapse between diagnosis and operation did not seem to influence the rate of fistula development. The study indicates that there is a two to three per cent risk of fistula development when a primary laryngectomy is performed. Fistula formation increased to about 10 to 12 per cent following radiotherapy, with an additional increase whenever previous operations on the neck had been done and/or if the disease demanded more extensive surgery. The study also indicates that the risk for fistula development is less when an experienced surgeon performs the operation.

[Patients dying in institutions. A medical and human challenge]. / Døende pasienter i institusjon. En medisinsk og menneskelig utfordring.

Over 40,000 people die in Norway every year. About 80% die in institutions and 2/3 are over 70 years old. The debate about terminal care and euthanasia is often based on unusual and extreme situations. The great challenge, however, is found in the quite ordinary routine conditions in our hospitals and institutions for the elderly. The continuing debate concerning active euthanasia hides several realities; fear of disease, worry about physical and mental disability, loss of dignity and autonomy and concern about dependence and helplessness in the last phases of life. Resolving some of these issues requires that the physician is aware of the true condition of the patient and communicates this knowledge in a caring and respectful manner. The patients' wishes must be weight against appropriate treatment.

Radiation in combination with intra-arterial infusion therapy with dacarbazine for metastatic malignant melanoma localized to a lower extremity.

Fourteen patients with metastatic malignant melanoma localized to a lower extremity were treated with combined radiotherapy and intra-arterial infusion therapy with dacarbazine. All lesions that were included in radiation fields regressed completely. Two patients relapsed within radiation fields and six relapsed elsewhere. One patient had a serious intimal lesion caused by the catheter.

Bilateral diffuse uveal melanocytic proliferation and uterine cancer. A case report.

PURPOSE: To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP), a rare paraneoplastic syndrome causing visual loss in patients with systemic carcinoma. RESULTS: A 70-year-old woman developed visual symptoms 13 months after surgery and local irradiation therapy for uterine cancer. Following bilateral external beam irradiation supplemented with subsequent drainage of subretinal fluid in the left eye, the visual acuity improved from 0.01 to 0.15 in this eye only. The visual acuity remained at this level until she died 4 1/4 years after the onset of eye symptoms. CONCLUSION: This is the fourth case that survived longer than 24 months after the onset of visual symptoms of the 22 previously reported cases with BDUMP. It demonstrates that radiotherapy may have a vision-preserving effect in this group of patients. The patient also developed two different paraneoplastic phenomena--a nephrotic syndrome before and BDUMP after treatment for uterine cancer.

Treatment of T3 laryngeal carcinoma. Clinical evaluation after 50 Gy, is it of any value?

29 patients with T3 carcinoma of the larynx were evaluated after irradiation with 50 Gy with special emphasis on the mobility of the vocal cord. 10 of the patients with fixation of the vocal cord were assumed to have unsatisfactory response to treatment and were therefore advised laryngectomy. In 4 of the patients the fixation was due to fibrosis. One patient also had a fixed vocal cord, but was discarded from the investigation because of inoperable regional metastases. 18 patients with improved mobility of the vocal cord continued the irradiation to 70 Gy. 6 of these patients later developed local recurrences. It is concluded that the mobility of the vocal cord after 50 Gy is of dubious prognostic value.

External radiotherapy for circumscribed choroidal haemangiomas using a modified retinoblastoma technique.

This report describes two cases of circumscribed choroidal haemangiomas involving the fovea, complicated by serous retinal detachment. Laser photocoagulation, generally accepted as the treatment of choice for choroidal haemangioma, was considered either to be of no visual benefit or a risk for jeopardizing vision further due to the subfoveolar lesions. Fractionated radiotherapy using a lens-sparing, modified retinoblastoma technique, was given, using circular fields of 15 mm diameter. The dose was 24 Gy in 8 fractions. In both eyes the retina reattached completely. The visual acuity improved markedly in the first, and was restored to the prior level in the second. Normalization of a high intraocular pressure was also achieved in the second case. We believe this method to be a reasonable and effective therapy for some choroidal haemangiomas after careful individual consideration.

Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodular basal cell carcinoma: a one-year follow-up study.

Fifty-eight patients with 119 nodular (2 mm or more in thickness) basal cell carcinomas successfully treated with photodynamic therapy were included in this 1-year follow-up study. The initial cure rate at 3-6 months was 92% after photodynamic therapy, which included an initial debulking procedure and topical application of dimethylsulphoxide in order to enhance penetration of 5-aminolevulinic acid (20% in cream) to which the lesions were exposed for 3 h prior to exposure to light. At examination 12-26 months (mean 17 months) after treatment 113 lesions (95%) were still in complete response. Six lesions (5%) had recurred, located on the face, scalp and ear. The cosmetic outcome was evaluated as excellent to good in 91%. Microscopic examination of biopsies taken from healed areas in 7 patients did not reveal any sign of damage in 5 and only minor alterations in 2.

External beam irradiation therapy for choroidal haemangiomas. Visual and anatomical results after a dose of 20 to 25 Gy.

PURPOSE: To evaluate the visual and anatomic results of radiation therapy in ten patients with choroidal haemangiomas. METHODS: Nine patients with circumscribed choroidal haemangiomas and one with diffuse choroidal haemangioma have been reviewed retrospectively. They were treated by lens-sparing external beam radiation therapy (20--24 Gy) (9 eyes) and plaque brachytherapy (25 Gy) (1 eye), respectively. RESULTS: The visual acuity improved by two lines or more in 8 of 10 eyes. No eyes showed deterioration of visual acuity. In all cases the retinal detachment showed complete resolution. A regression in tumour thickness was observed in all cases, and a reduction of anisometropia in cases with submacular infiltration by the tumour. During follow-up (0.4--8.8 years) there were no signs of radiation cataract, retinopathy or optic neuropathy. CONCLUSIONS: External beam radiation (20--25 Gy) is a reasonable alternative for treatment of symptomatic choroidal haemangiomas.

Computed tomography in T1 carcinoma of the larynx.

The findings at computed tomography (CT) were reviewed in 33 patients with laryngeal carcinoma classified as T1 at clinical examination. CT revealed extralaryngeal growth and thus changed the classification to T4 in 6 of the 20 patients with a supraglottic primary tumor, but in none of the 13 patients with a glottic tumor.

Brachytherapy of squamous cell carcinoma of the nasal vestibule.

From 1985 to 1994, 23 patients with squamous cell carcinoma of the nasal vestibule were treated by brachytherapy. The TNM stage was as follows: T1N0 (9 patients), T2N0 (11 patients) and T4N0 (3 patients). Four patients had primary surgery and postoperative brachytherapy, whereas 12 patients had brachytherapy alone and 7 had tele- and brachytherapy in combination. For brachytherapy, the plastic tube technique was used. With the exception of one patient with a partial response, complete response was obtained in all patients. Two patients relapsed: one (T4N0) locally after 5 months and one (T2N0) regionally after 12 months. Both are alive and with no evidence of disease after salvage surgery. For early stage carcinoma (T1, T2) of the nasal vestibule, brachytherapy is a safe treatment yielding a high grade of local control and with good cosmetic results.

Value of routine follow-up in patients treated for squamous cell carcinoma of the head and neck.

The records of 214 consecutively registered, previously untreated patients with squamous cell carcinoma of the head and neck region were reviewed. Among the 157 patients considered "free of disease" following the primary treatment 54 developed recurrences - all but three within three years. Only in patients with carcinoma of the larynx treated with radiation alone did follow-up disclose recurrences for which further treatment resulted in a significant number of cures. For these patients the cure rate was one in 79 routine appointments compared to only one cure in 325 appointments for patients with carcinoma in other localizations. It seems that our routine follow-up procedure for most types of carcinoma is too extensive and that follow-up beyond three years mainly will be of value for the possible detection of second primary malignancies.

Photodynamic therapy of residual or recurrent basal cell carcinoma after radiotherapy using topical 5-aminolevulinic acid or methylester aminolevulinic acid.

This study was conducted to assess the efficacy of aminolevulinic acid-based photodynamic treatment for residual or recurrent basal cell carcinomas after radiotherapy. Photodynamic therapy with either topical 5-aminolevulinic acid 20% and dimethylsulfoxide 99% pretreatment or topical methylester aminolevulinic acid 20% w/w in cream and subsequent light illumination of 50-200 J/cm2 was performed after an initial skin shaving procedure in 20 patients with 22 residual or recurrent basal cell carcinomas. Three lesions were treated once, while twelve, three, one and two lesions received two, three, four and five treatment sessions respectively. At examination, 6-40 months (mean 22 months) after the last treatment, 18 lesions were in complete remission. All lesions were considered excellent or good with regard to cosmetic outcome. Three lesions responded only partially to photodynamic therapy and a fourth lesion recurred 21 months after photodynamic treatment. Two of these four lesions were confirmed as the morpheaform type of basal cell carcinoma.

Treatment of malignant metastatic midgut carcinoid tumours with recombinant human alpha2b interferon with or without prior hepatic artery embolization.

Nineteen patients with histologically verified midgut carcinoid tumours and liver metastases were included in a prospective study with daily recombinant human alpha 2b interferon injections of 5 million IU subcutaneously for 1 year. All had as much as possible of the primary tumour removed at laparotomy. Whenever technically possible (in seven cases), an embolization of the hepatic arteries was performed before interferon start. The response rate of the combined embolization and interferon treatment (n = 7) was 86% after 1 year, as judged from either a 50% reduction in excretion of 5-hydroxy-3-indoleacetic acid in the urine or a 50% reduction in the area of the largest liver metastasis as evaluated by computed tomography. All patients experienced an improvement in diarrhoea and/or flushing. When interferon was given alone (n = 12), 40% responded on the basis of objective criteria (50% after 6 months), whereas an improvement in either diarrhoea or flushing was experienced by 70% (75% after 6 months). In this group one patient had died and one had decided to withdraw after 6 months, at which time both were responders. We conclude that interferon seems to be an effective treatment of malignant metastatic midgut carcinoid tumours and that embolization of the liver arteries seems to increase the response rate, as judged after 1 year.

Elective radiotherapy of the neck in patients with squamous cell carcinoma of the head and neck.

A prospectively recorded 5-year series of 254 patients receiving elective neck irradiation is evaluated. All had clinically negative necks and initial control at the primary site. Forty-seven percent of the patients had T3-4 tumours. Radiotherapy was delivered from a megavolt source at 2 Gy/day 5 days a week to a total dose of 46-50 Gy. All but 3 patients completed the treatment as planned. Neither tumour stage nor site of the primary tumour was related to the incidence of regional recurrences. Of 30 patients receiving 46-49 Gy, 5 died from neck node recurrences. Of 221 patients treated to 50 Gy or more, 16 (7.2%) developed regional recurrences. Two of these recurrences were avoided, giving a regional failure rate of 6.3%. As a whole, 7.8% died from regional, 11.4% from local, and 3.1% from distant recurrences.

Combined radiotherapy and surgery in the treatment of neck node metastases from squamous cell carcinoma of the head and neck.

A prospectively recorded series of 107 patients with clinical neck node metastases from head and neck squamous cell carcinomas, treated in 1983-1988, and with initial local control, is evaluated. Eighty-eight patients received preoperative, and were operated 4-6 weeks after radiotherapy, and 19 received postoperative radiotherapy. Forty-four of the neck specimens in the preoperatively treated patients showed vital tumor tissue, 7 with positive and 37 with negative resection margins. Nine of the latter 37 patients died due to regional recurrence. Twenty-three of the preoperatively treated patients had no palpable residual tumor following radiotherapy, but histological examination showed vital tumor tissue in five, of whom two had N1 neck disease. The overall regional failure rate was 19%. Eleven patients (10%) died from local recurrence and 11 from distant metastases. Forty-one patients (38%) are alive without evidence of disease and three (3%) alive with disease (mean observation time 30 months). Combined treatment is recommended for all cases of neck node metastases.