Dose-escalation with CHARTWEL (continuous hyperfractionated accelerated radiotherapy week-end less) combined with neo-adjuvant chemotherapy in the treatment of locally advanced non-small cell lung cancer.

PURPOSE: a radiation-dose-escalation study was undertaken to assess the therapeutic benefit of combining accelerated hyperfractionated radiotherapy (RT) with neo-adjuvant chemotherapy (CT) in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: One hundred and thirteen patients with locally advanced NSCLC were entered into a phase II trial of CHARTWEL (CHART Week-End-Less) 54 Gy or 60 Gy with or without three cycles of CT. Acute oesophageal reactions and analgesia were scored for up to 8 weeks after the start of RT. Pneumonitis, lung fibrosis, spinal cord and oesophageal strictures, were assessed using clinical and radiological criteria from 3 months onwards and throughout the study. Haematological and gastrointestinal toxicity was monitored in those patients undergoing CT. Endpoints for treatment outcome were overall survival, disease-free survival and loco-regional control. RESULTS: Chemotherapy enhanced the incidence and duration of acute dysphagia,but the increase was transient. Healing occurred in all cases and there has been no evidence of long-term oesophageal complications. Clinically, almost 25% of those receiving CT+RT had Grade 2 pneumonitis, higher than seen with RT alone. However, the 1 patient with severe Grade 3 pneumonitis was in the RT 60 Gy alone group. An incidence of 17% Grade 2 pulmonary fibrosis at 2 years was seen with CT, slightly lower than with RT alone. To date, there is no evidence of Grade 3 lung fibrosis. There was a higher scoring of lung damage with the radiological endpoint, which gave no indication that CT increased pulmonary toxicity over that of RT alone. Loco-regional control at 2 years was 37% and 55% for CHARTWEL 54 Gy and 60 Gy alone compared with 72% in those treated with 60 Gy and neo-adjuvant CT However, this did not translate into a survival advantage. CONCLUSIONS: This study of CHARTWEL combined with induction chemotherapy, has shown that the strategy is feasible and that a possible therapeutic benefit may be obtained by the addition of CT. Although neo-adjuvant treatment increased acute mucosal reactions and slight-to-moderate pneumonitis seen with CHARTWEL 60 Gy, the clinical management and quality of life of these patients is similar to those treated with radiotherapy alone.

Experience with dose escalation using CHARTWEL (continuous hyperfractionated accelerated radiotherapy weekend less) in non-small-cell lung cancer.

Results from the multicentre randomized trial of CHART (continuous, hyperfractionated, accelerated radiotherapy) in non-small-cell lung cancer (NSCLC) showed a significant increase in survival (P=0.004) compared with conventional radiotherapy and a therapeutic benefit relative to late radiation-induced morbidity. However, 60% of patients died because of failure to control locoregional disease. These findings have stimulated interest in assessing the feasibility of dose escalation using a modified CHART schedule. Acute and late morbidity with a CHARTWEL (CHART WeekEnd Less) schedule of 54 Gy in 16 days was compared with that observed with 60 Gy in 18 days in patients with locally advanced NSCLC. The incidence and severity of dysphagia and of analgesia were scored using a semiquantitative clinical scale. Late radiation-induced morbidity, namely pulmonary, spinal cord and oesophageal strictures, were monitored using clinical and/or radiological criteria. Acute dysphagia and the analgesia required to control the symptoms were more severe and lasted longer in patients treated with CHARTWEL 60 Gy (P< or = 0.02). However, at 12 weeks, oesophagitis was similar to that seen with 54 Gy and did not lead to consequential damage. Early radiation pneumonitis was not increased but, after 6 months, there was a higher incidence of mild pulmonary toxicity compared with CHARTWEL 54 Gy. No cases of radiation myelitis, oesophageal strictures or of grade 2 or 3 lung morbidity have been encountered. CHARTWEL 60 Gy resulted in an enhancement of oesophagitis and grade 1 lung toxicity compared with CHARTWEL 54 Gy. These were of no clinical significance, but may be important if CHARTWEL is used with concomitant chemotherapy. These results provide a basis for further dose escalation or the introduction of concurrent chemotherapy.

Meningeal myeloma in the absence of systemic disease, and as the initial feature of disease progression.

We describe a 60-year-old man with stage IIA myeloma, who despite achieving a systemic remission after C-VAMP, progressed with isolated meningeal myeloma. Meningeal involvement in myeloma is a rare complication with a poor prognosis.

Chest radiography or computed tomography in the assessment of lung cancer prior to radiography.

A series of 93 patients with lung cancer were considered for intensive radiotherapy, and investigated by chest radiography and computed tomographic (CT) scan. Spread of tumour was detected radiologically to lymph nodes, pleura or chest wall on 98 occasions. Of these, 16 were shown by both investigations, but in 82 the spread was revealed only by CT examination. Clear visualization of the tumour prior to radiotherapy is important to select those patients who would benefit from radical radiotherapy, to allow accurate treatment planning, and to allow, in subsequent follow-up, monitoring of the response to radiotherapy. In this study tumour was clearly visualized in 59 patients treated, but in 31 (53%) of these only by the use of computed tomography.

Chest radiography or computed tomography to assess the response of lung cancer to radiotherapy.

In 58 patients with lung cancer the response of the primary tumour to treatment with CHART was followed by both chest radiograph and computed tomographic (CT) scan. Clear evidence of complete response was seen by chest radiograph in 11 patients and by CT scan in 20. If all studies showing no definite tumour, regardless of the quality of the study, were included then complete response was considered to have occurred in 25 as indicated by chest radiograph and in 22 by CT scan. The validity of the observations was tested by life table analysis comparing the survival of those showing complete regression with those whose response was incomplete. Comparison based on the CT scan findings showed the greatest significance (P = 0.0001), while that based on the chest radiograph findings showed the least (P = 0.044).