Limited field irradiation in early stage (T1-2N0) non-small cell lung cancer.

BACKGROUND AND PURPOSE: Radiotherapy can effectively control non-small cell lung cancers (NSCLC) of limited size. This study is conducted to investigate whether limited field irradiation, without irradiation of regional lymph nodes, can safely be used in these patients. MATERIALS AND METHODS: Between 1988 and 1993, 31 patients with operable T1-2N0 NSCLC received radiotherapy (48 Gy in 12 fractions) to a limited ('postage stamp') field. The hilum and mediastinum were not included in the radiation portals. RESULTS: Overall survival was 42% at 3 years. Disease-specific survival at 3 years was 76%. One patient developed an isolated regional failure, one had a combined local and distant failure, one had a combined local, regional and distant failure, while three patients failed at distant sites only. Thus, only two patients (6%) recurred regionally. CONCLUSIONS: This study shows that 'postage stamp' irradiation is an effective alternative to surgery. Radiation of the hilar and mediastinal lymph nodes can be omitted in these pulmonary compromised patients.

[Radiotherapy following breast-conserving surgery: more local recurrences after longer delay]. / Radiotherapie na mammasparende operatie: na langer uitstel meer lokaal recidief.

OBJECTIVE: Evaluation of results of breast conserving therapy in early stage breast cancer and of importance of time interval between surgery and radiotherapy. DESIGN: Descriptive study. LOCATION: Free University Hospital, Amsterdam. METHOD: In the period 1980-1989, 554 patients with 560 invasive breast cancers were referred for radiotherapy after wide local excision of the tumour with axillary lymph node dissection. The dose to the breast was 50 Gy + 15 Gy boost dose. In case of positive margins, a higher boost dose (20-25 Gy) was given. Node-positive patients received adjuvant chemotherapy (premenopausal patients) or hormonal therapy (postmenopausal patients). RESULTS: The median follow-up period was 82 months (range 52-160 months). The 5 and 10-year survival rates were 86.7% and 72.6%, respectively. Local (breast) relapse occurred in 22 patients (3.9%). The breast recurrence rate was 8/329 (2.4%) for patients who started radiotherapy within 7 weeks after surgery, as against 14/231 (6.1%) for patients with a longer interval (p < 0.05). In Cox's proportional hazards analysis, age (negative relation), T-stage and interval between surgery and radiotherapy were identified as independent factors predictive of breast recurrence (p < 0.05). CONCLUSION: A delay of radiotherapy after breast conserving surgery of more than 7 weeks can adversely affect the local tumour control rate.

Results of radiotherapy and vitamin E in the treatment of Peyronie's disease.

PURPOSE: A retrospective analysis of 38 patients with Peyronie's disease treated with primary radiotherapy in the period of 1975-1993. METHODS AND MATERIALS: Important complaints were curvature of the penis during erection for 92% of the patients, painful erection for 68%, and problems with sexual intercourse for 37.5%. Average size of all indurated plaques was 2.5 cm. The average pretreatment duration of symptoms was 9.5 months. All 38 patients were irradiated with orthovoltage radiotherapy (200 and 250 kV photons) with a total dose of 9 Gy in 5 alternating days (regimen A). Because of minimal response, 16 patients were irradiated again with another 9 Gy in 5 days and finally received 18 Gy (regimen B). RESULTS: With regimen A, a satisfying improvement was achieved for the majority of the patients: 65% experienced less penile pain during erection, 40% reported less curvature of the penis, and 47% experienced an improvement of their sex life. With the higher dose of regimen B there was an additional improvement for a minority of the patients: 25% reported less pain during erection, 21% had less curvature, and 29% experienced an improved sex life. With regimen A, pain improvement was statistically significantly superior when compared to regimen B. For all other improvements (curvature, sexual intercourse, and induration) no dose-response relation could be demonstrated between regimen A and the higher dose regimen B. No patient experienced any radiation-induced morbidity. After evaluating regimen A and regimen B, the overall result was that 76% experienced less pain, 60% reported an improved sex life, and 48% had a diminished curvature during erection. CONCLUSION: From this analysis it can be concluded that the distressing symptoms of Peyronie's disease can be treated successfully with radiotherapy. Radiotherapy proves to be a safe, noninvasive treatment method without causing morbidity. Low-dose radiotherapy with only a few fractions is recommended for an effective treatment result.

Curative radiotherapy for technically operable stage I nonsmall cell lung cancer.

PURPOSE: Retrospective study of patients with Stage I nonsmall cell lung cancer (NSCLC) unable to undergo surgery or refusing surgery. METHODS AND MATERIALS: Between 1984 and 1990, 47 patients with technically operable Stage I NSCLC received hypofractionated radiotherapy. The total dose varied from 32 Gy in six fractions (two fractions/week) or 40 Gy split course in ten fractions (low-dose schedules) to 48 Gy in 12 fractions or 56 Gy in 20 fractions (high-dose schedules). The mean age of the patients was 75 years. Three patients refused surgery and 44 patients were inoperable due to their medical condition. Severe associated disease was present in 34 patients (72.3%). RESULTS: The intrathoracic recurrence rate was 25.5%. In a multivariate analysis, tumor size was identified as the only significant factor predictive for intrathoracic failure (p < 0.001). Disease-specific survival was 90, 53, and 32% at 1, 3, and 5 years, respectively. In Cox's proportional hazards analysis, only tumor size was predictive for disease-specific survival. Overall survival (all causes) was 70, 33, and 15% at 1, 3, and 5 years, respectively. In Cox's proportional hazards analysis, only the presence of severe associated disease was predictive for overall survival (p < 0.01), while tumor size did not attain statistical significance (p = 0.08). There were no severe acute or late side-effects. CONCLUSION: Radiotherapy can effectively control small nonsmall cell tumors. The reported results are comparable to those achieved with more fractionated radiation schedules. In patients of age or in poor medical condition, hypofractionated radiotherapy can be given with curative intent, with minimal burden to the patient.

Importance of timing of radiotherapy in breast conserving treatment for early stage breast cancer.

This study reports on the treatment results in 508 patients with 514 AJCC stage I-II invasive breast carcinomas treated between July 1980 and July 1989. All patients underwent a lumpectomy with axillary lymph node dissection with postoperative irradiation. Adjuvant chemotherapy was given to premenopausal node-positive patients. Postmenopausal node-positive patients received adjuvant hormonal treatment. The median follow-up period was 68 months (range, 40-152 months). The 5-year survival rates were 92.6%, 81.4% and 65.5% for stage I, stage IIA and stage IIB, respectively. Distant metastases were the main cause of death. Locoregional failures occurred in 4.9%. Breast recurrences were detected in 17 patients (3.3%). In a Cox proportional hazards analysis, T-stage, pathological margins and interval between surgery and radiotherapy were identified as independent factors predictive of breast recurrence (p < 0.05). The results suggest that radiotherapy should be initiated early after surgery to maintain the breast recurrence rate as low as possible.

Consolidative thoracic radiotherapy and prophylactic cranial irradiation in limited disease small cell lung cancer.

Between 1983 and 1990, 128 patients with limited disease small cell lung cancer (SCLC) received consolidative thoracic irradiation after reaching a complete (CR) or partial response (PR) to combination chemotherapy. Patients in CR (n = 85) received 35-36 Gy in 12-14 fractions and patients in PR (n = 43) 24-30 Gy in 3-6 fractions. Until 1989, prophylactic cranial irradiation (PCI) was given to patients in CR. There was no significant difference in survival between the CR and PR group. However, patients with residual tumor detected by radiology or bronchoscopy or cyto-/histology had significantly longer survival than those with residual tumor demonstrated by more than one of the above methods of investigation. Overall, local progression was observed in 22% and distant dissemination in 63% of patients. The rate of brain metastases was significantly lower in patients treated with methotrexate and nitrosurea containing schedules and PCI, compared to those who were treated with other schedules (irrespective of PCI).

Hypofractionated radiation therapy in the treatment of superior vena cava syndrome.

We retrospectively reviewed 46 patients with superior vena cava syndrome during the period 1986-1992. The common symptoms included congestion of collateral veins of the neck, anterior chest wall, face, eyelids and right arm. Dyspoea and cyanosis occurred less frequently. In all but two patients a histological diagnosis was made by invasive and non-invasive examination without complications. In 82% of all patients a primary lung carcinoma was the cause of the superior vena cava syndrome. For 39 patients radiotherapy was the first treatment of choice. To relieve the distressing symptoms patients received one of two regimens employing hypofractionated radiotherapy. In regimen 3F, 25 patients received three weekly high dose fractions of 8 Gy delivering a total dose of 24 Gy. Regimen 2F, applied to seven patients, consisted of two weekly fractions of 8 Gy, giving a total of 24 Gy. In both regimens a good palliative result was established, however the results of the 3F regimen were superior. Using the 3F regimen a partial response was obtained in 96% of all patients, and 56% achieved a complete response. With the 2F regimen a partial response was achieved in 70% of all patients, and a complete response in only 28%. Minimal side effects were noted. After reviewing our experience, the 3F regimen is recommended for rapid and effective relief of the superior vena cava syndrome.

Hypofractionation radiotherapy for a locally recurrent rectal carcinoma as a treatment for an elderly patient.

A very old patient, who had been suffering from rectal carcinoma for many years without achieving a complete response to electrocoagulations, was given palliative radiotherapy by hypofractionation with a total dose of 30 Gy in 3 weeks, 1 fraction a week. A complete response was achieved. No special therapy-related morbidity was noted. After the radiotherapy, an acceptable quality of life was maintained for 12 months without a local recurrence. It is concluded that radiotherapy may be a simple and efficient method of palliation without distressing morbidity compared with electrocoagulation.

[Palliative radiotherapy in non-small cell bronchial carcinoma]. / Palliatieve radiotherapie bij het niet-kleincellige bronchuscarcinoom.

OBJECTIVE: Evaluation of palliative radiotherapy for patients with non-small cell lung cancer. DESIGN: Descriptive study. LOCATION: University hospital Vrije Universiteit, Amsterdam. METHOD: Between 1987 and 1991, 146 patients with stage IIIB or IV non-small cell lung cancer received palliative radiotherapy for symptoms of intrathoracic tumour growth. There were 144 evaluable patients and all of them received three fractions of 800 cGy (1 fraction per week). RESULTS: Median survival was 6.3 months for stage IIIB and 4.2 months for stage IV patients (p < 0.005). Stage IIIB patients with a Karnofsky performance score of 70 and above showed significantly (p < 0.01) longer survival than those with a performance score below 70. Local progression was recorded in 61.1% of patients. However, 68.8% of the patients were free of local progression for at least 75% of their remaining survival time. The toxicity of the treatment was acceptable. CONCLUSION: On the basis of these results and results of other studies, it is concluded that the palliative effect of a small number of sessions with high fraction doses is comparable with that achieved with a more fractionated schedule. A short course of radiotherapy is preferable to minimize inconvenience for the patient as well as for the radiotherapy department.

Hypofractionated radiation therapy in unresectable stage III non-small cell lung cancer.

BACKGROUND: Hypofractionation is the current choice for radiation therapy for patients with unresectable non-small cell lung cancer (NSCLC) at the authors' institute. METHODS: In this nonrandomized study, three hypofractionated radiation schedules (40-Gy split course; 30-32 Gy in 6 fractions and 24 Gy in 3 fractions) are evaluated in 301 patients with unresectable Stage III NSCLC: RESULTS: Patients with Stage IIIA disease treated with a 40-Gy split course had longer survival (P < 0.005) and a lower local relapse rate (P < 0.01), but a higher distant failure rate (P < 0.01) than those receiving 24-32 Gy. Survival for patients with Stage IIIA disease treated with 40 Gy at 1, 2, and 5 years was 47%, 22%, and 7%, respectively. For patients with Stage IIIB disease, the radiation scheme used did not correlate with survival and relapse rates. Survival at 1, 2, and 5 years was 30%, 9%, and 2%, respectively. The hypofractionated radiation schemes were well tolerated, and no severe complications were recorded. CONCLUSIONS: In patients with Stage IIIA disease, 40-Gy split-course radiation therapy yields survival rates comparable to those achieved with conventional radiation therapy. In patients with Stages IIIB and IV NSCLC, 24 Gy in 3 weekly fractions yields survival rates comparable to those achieved with higher total doses given in more fractions.

[Radiation injury presenting as tumor recurrence following irradiation for non-small-cell bronchus carcinoma]. / Stralingsschade zich voordoend als tumorrecidief na bestraling wegens een niet-kleincellig bronchuscarcinoom.

Case records of two irradiated patients, each with an inoperable non-small cell carcinoma of the bronchus, are presented. After an initial period of 1.3 and 2.3 years, respectively, of regression of the tumour symptoms occurred, viz. severe pain due to multiple rib fractures in one and a superior vena cava syndrome in the other, suggestive of tumour regrowth. Careful comparison of results of all radiographic images and radiotherapy data suggested osteoradionecrosis as the cause of the rib fractures in one patient. The long time interval and the stabilization of the symptoms in the other made tumour regrowth unlikely. The so called late tissue reaction after radiotherapy as a possible cause of symptoms in both patients is discussed.

Ethmoid and upper nasal cavity carcinoma: treatment, results and complications.

From 1970 to 1985, 45 patients with carcinoma of the upper nasal cavity and ethmoid sinuses were radically treated. The tumor parameters, treatment strategy, radiotherapy technique and the results of treatment of these patients are retrospectively analysed in this study with particular reference to complete blindness as a major complication. In most cases tumor was removed by meticulous surgical dissection, and thereafter quality-controlled radiation therapy (external therapy: mean dose 65 Gy in about 7 weeks, or external therapy with brachytherapy boost: mean dose 82 Gy in about 10 weeks) was used for this group of patients. The results show 68% recurrence-free survival at 5 years, adjusted for intercurrent deaths. Complications of treatment were seen in seven patients (16%) who developed eye damage with some loss of visual acuity, none however leading per se to complete blindness. It may be concluded that blindness may be avoided to a major extent while treating carcinomas in the nose-ethmoid areas without compromising loco-regional control.

A critical look at the TNM classification for laryngeal carcinoma.

A total number of 564 patients with glottic (427) and supraglottic (137) laryngeal carcinoma was prospectively staged clinicoendoscopically (CS) and radiologically (RS). These patients were treated from 1974 to 1985 with quality-controlled high-dose radiation therapy. The validity of CS versus RS was checked in this study with the parameter of recurrence-free adjusted survival (RFADS) at 3 and at 5 years. It appears that RS is more valid and has therapeutic implications in planning the target volume for irradiation. The CS should be regarded as inadequate for radiotherapeutic considerations. The International Union Against Cancer (UICC) 1987 norms for staging laryngeal carcinoma (clinical, endoscopic, and imaging) should be strictly followed.

Phase II trial of combined radiotherapy and daily low-dose cisplatin for inoperable, locally advanced non-small cell lung cancer (NSCLC).

With the use of cis-diamminedichloroplatinum(II), cisplatin, to enhance the effect of radiation a combined modality approach was designed to treat patients with inoperable, locally advanced NSCLC. The regimen consisted of radiation doses of 300 cGy for 4 days every week for 4 weeks with a 2 week split in between. Each radiation dose was followed by an i.v. injection of cisplatin 6 mg/m2 within 30 min. Hydration consisted on an oral fluid intake of 2 L only, enabling the patient to receive the treatment on an outpatient basis. Of 40 patients entered into the study, 37 were evaluable for toxicity and 33 for response. Overall response rate was 65% and complete response rate 22%. Median duration of local control was 7 months. The majority of all patients (76%) eventually progressed at the primary tumor site, while in 16 patients relapse occurred in distant sites first. Median duration of overall survival was 10.5 months, whereas that of complete responders was 29.5 months. Generally, acute side effects were transient and did not require discontinuation of treatment. One patient presented with thrombocytopenia 4 weeks after treatment had been finished. His death of cerebral bleeding was likely to be related with his therapy-resistant malignancy. Of late side effects three patients showed disabling symptoms consisting of uncontrollable pulmonary infections in the presence of tumor in two patients, one patient had radiation myelopathy and another experienced vertebral collapse with distal paresis. The combination of radiation and daily low-dose cisplatin is a tolerable treatment modality with most benefit for patients reaching a complete remission. Intensification of the regimen is being planned in those patients with inoperable, locally advanced squamous cell lung cancer to reach a complete remission.

Radiation therapy for advanced (T3T4N0-N3M0) laryngeal carcinoma: the need for a change of strategy: a radiotherapeutic viewpoint.

Since 1974 through 1984, 137 selected patients with loco-regionally advanced carcinoma of the larynx (T3T4 N0-N3) were treated primarily with quality controlled high dose megavoltage radiation therapy with salvage surgery in reserve. This policy of treatment has yielded 67% loco-regional control probability with primary radiotherapy and 85% with salvage surgery at 3 years. Fourteen patients (14/38) had moderate to severe complications after salvage surgery. The quality of life of the patients successfully treated by radiation therapy is obviously and unquestionably better. Primary radiotherapy with salvage surgery in reserve should be accepted as the strategy of choice in at least a selected group of patients with advanced laryngeal carcinoma.

Heterogeneity of stage II glottic carcinoma and its therapeutic implications.

The heterogeneity of glottic carcinoma results in variable loco-regional control probabilities from 40 to 80%. These widely different results may be due to two prognostic parameters of the tumor: the mobility of the vocal cord and the volume of the tumor. On the other hand radiation dose and technique may influence the treatment results. Stringent work-up has been prospectively undertaken in 156 patients with Stage II glottic carcinoma since 1974 through 1983 in the Academic Hospital of the Free University in Amsterdam. Several subgroups were defined from the beginning to indicate one or both of these prognostic factors. All were treated with a high quality accurate radiation therapy program delivering high dose to all patients with worse prognostic factors and even higher dosages to voluminous tumors with impaired mobility of a cord or slowly regressing tumors. The latter was individually judged for each patient towards the end of the treatment period. The loco-regional control probability of around 80% for all the subgroups irrespective of the prognostic factors indicate that the heterogeneity of Stage II glottic cancer may be influenced by high dosages of quality controlled radiotherapy. Thus results hitherto reported in literature may be further improved by the dose-schedules outlined here.

Long-term results of concurrent polychemotherapy and radiotherapy in patients with stomal recurrence after total laryngectomy.

From 1978 through 1985, eight patients with stomal recurrence after total laryngectomy were treated with a combination of a cytotoxic regimen (vincristin sulfate, bleomycin, and methotrexate [VBM]) and radiotherapy. The essential feature of this combination is the synchronous administration of pulses of VBM and fractionated doses of external radiotherapy in order to achieve potentiation of radiotherapy. On average, four to five pulses of VBM were given. Severe mucositis is the main problem during treatment. Two patients needed nasogastric tube feeding, and treatment was carried out as an inpatient procedure. Five patients are alive with complete local remission at 7 years, 3 years, 2 1/2 years, 14 months, and 8 months after treatment. These results appear to be spectacular, even though the number of patients is small. Of the three patients who died, only one had recurrent disease around the tracheostoma. The two other patients were free of disease in the neck when they died 6 and 16 months after treatment of, respectively, lung metastases and a second primary tumor in the lung. Patients with stomal recurrence after total laryngectomy are now routinely treated with synchronous VBM and radiotherapy.

Feasibility study on daily administration of cis-diamminedichloroplatinum(II) in combination with radiotherapy.

In experimental models cis-diamminedichloroplatinum(II) (cis-platinum) showed to have a radioenhancing effect. The feasibility of daily administration of cis-platinum in combination with radiotherapy was studied in 21 patients with locally advanced inoperable cancers (head and neck 7, esophagus 5, bronchus 3 and others 6). The tumours were squamous cell (15), or adenocarcinoma (6). Radiotherapy was delivered in one (180 cGy; 5 patients) or two (each of 125 cGy; 16 patients) fractions per day to a cumulative dose of 3000-6800 cGy, while cis-platinum was administered at a total daily dose of 8 mg/m2 (14 patients) or 6 mg/m2 (7 patients), in one single or two divided injections (total dose 168-352 mg cis-platinum). Fourteen patients received a total daily cis-platinum dose of 8 mg/m2 with 4 l of i.v. hydration. Severe myelosuppression occurred in 10/14 patients (range white blood cell count nadirs 0.6-2.1 X 10(9)/l) after 3-5 weeks of treatment, while seven developed severe thrombocytopenia (less than 75 X 10(9)/l). All patients became anaemic. Due to this myelosuppression, radiation treatment had to be postponed in four patients for 18-35 days. Eight patients developed bronchopneumonia, two of them had a septicaemia and one died. One patient with a bronchial carcinoma developed necrotizing pneumonitis with a cavity outside the tumour area and subsequent severe pulmonary fibrosis within the radiation field. Seven patients received cis-platinum at 6 mg/m2 per day without i.v. hydration. A moderate leukopenia (white blood cell count nadirs 1.8-2.1 X 10(9)/l) was observed in three patients requiring postponement of treatment in one of them.(ABSTRACT TRUNCATED AT 250 WORDS)

The quality of voice in patients irradiated for laryngeal carcinoma.

Data from 150 patients with laryngeal carcinoma, consecutively treated primarily by radiotherapy from 1965 through 1974 was analyzed to assess the quality of voice. The voice appears to improve in majority of the successfully irradiated patients. In 76% of the evaluable patients in this group, the quality of voice appears to have attained normalcy or near normalcy. Smoking appears to have a negative influence. High incidence of bronchogenic carcinoma along with the negative influence of smoking on the quality of voice in this series of patients indicate that the patients should be advised against smoking in day-to-day clinical practice.