Alternating radiotherapy and chemotherapy schedules in limited small cell lung cancer: analysis of local chest recurrences

doi:10.1016/0167-8140(91)90142-4

Radiotherapy and Oncology

Volume 20, Issue 2, February 1991, Pages 91-98

https://doi.org/10.1016/0167-8140(91)90142-4 Get rights and content

Abstract

An analysis of the chest recurrences was conducted in 72 consecutive patients with limited small cell lung cancer treated in two successive phase II trials alternating six induction chemotherapy courses and three series of thoracic radiotherapy, followed by maintenance chemotherapy. The total radiation dose was 45 Gy (3 series of 15 Gy) in the first trial, and 55 (20, 20 and 15 Gy) in the second. The effect of the irradiated volume was investigated by comparing the local relapse rates in the group of patients treated by radiation fields encompassing the initial tumor volume to another group in which the initial target volume was not fully covered by radiation fields. The definition of these two groups was performed retrospectively by examination of radiological, fiberoptic bronchoscopy initial findings, technical radiation charts and check films. The local recurrence rate were 33 and 36% in each group (no significant difference). This finding could suggest that tumor shrinkage after chemotherapy might allow the use of “reduced” radiation volumes. However, the limited number of patients does not permit a definite conclusion. The effect of radiation dose was investigated by comparing the local control rates in the two consecutive trials which delivered 45 and 55 Gy, respectively. No difference in long-term local control was found: the addition of 10 Gy in the second trial only seemed to delay the appearance of local recurrences by 6 months. Twenty percent of patients died from a local relapse without evidence of distant metastases. If the metastasis rate of 50% found in the whole series is assumed in this subset, 10% of patients could actually benefit from optimal local management. These findings stress the need to investigate more effective loco-regional therapies in limited small cell lung cancer.

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Curative therapy for patients with small-cell lung cancer (SCLC) is based on multidrug chemotherapy combinations and radiotherapy. After a long time follow-up, the aim of the study was to evaluate the efficacy and toxicity of sequential chemo-radiotherapy and the effect of prophylactic cranial irradiation (PCI).
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After a median follow-up of 78.6 months, 20 patients remained alive (20.8%, median survival time 18.2 months). The 2-/5-year overall survival rates were 33.8% and 12.6%, the 2-/5-year loco-regional control rates were 30.3% and 24.5%, respectively. Distant metastases occurred in 43 patients (24 cerebral). Cerebral metastasis occurred in 6.7% and 27.2% of the patients with PCI and without PCI respectively. Only tumor stage showed a statistically significant impact on overall survival and loco-regional control in multivariate analysis. Radiotherapy was well tolerated. Grade 3/4 toxicity occurred in seven patients. Prognosis of patients with SCLC remains poor. Administration of PCI in selected patients bears a decrease in the incidence of cerebral metastases. Alternative chemotherapy schemes as well as irradiation schemes and techniques should be the substance of future randomized trials.
Le traitement du cancer bronchopulmonaire à petites cellules repose sur l’association d’une polychimiothérapie et d’une radiothérapie. L’objectif de cette étude était d’évaluer l’efficacité et la toxicité de la séquence thérapeutique chimiothérapie–radiothérapie suivi d’une irradiation prophylactique de l’encéphale.
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Small-cell lung carcinomas (SCLC) represent less than 20% of all lung cancers. As it is an aggressive tumour, on account of its high and early risk of dissemination, only a third of patients have limited-stage disease at diagnosis. For these patients, the current state-of-the-art treatment involves cisplatin–etoposide chemotherapy combined with chest radiotherapy. Because of the high risk of brain metastases, prophylactic cranial irradiation (PCI) is indicated in good responders and should be part of the standard management of these patients on the basis of a PCI meta-analysis showing a 5% increase in survival at 3 years. The 5-year survival rate reaches 25% in the best series. This progress is subsequent to a better combination of polychemotherapy and both thoracic and cerebral irradiation. In extensive disease, radiotherapy has also a place in the management of SCLC: PCI reduces the risk of brain metastases and significantly improves overall survival, so that cisplatin (or carboplatin)–etoposide followed by PCI in responding patients has become the standard treatment. Many issues are subject for further clinical research concerning timing, volume and schedule of thoracic radiotherapy to be used in combination with chemotherapy regimen. Progress in thoracic radiotherapy can only be achieved by including patients in prospective studies.
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A study by Arriagada et al. [42] compared target volumes, including a 1–1.5 cm margin to target volumes with less than 1 cm margin. No difference was found in local recurrence rates between the two arms [42]. The results of these three studies suggest that it is appropriate to treat the post-chemotherapy tumour volume.
Thoracic radiotherapy has an established role in the management of limited-disease small-cell lung cancer (LD SCLC). However, essential questions relating to the optimisation of thoracic radiotherapy remain unanswered, including volume of irradiation, optimal total dose, fractionation, timing and sequencing of radiation. This review highlights the need for well-designed multi-national trials aimed at the optimisation and standardisation of radiotherapy for LD SCLC.
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^☆: Presented at the 7th ESTRO meeting in The Hague, September 5–8, 1988.

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Alternating radiotherapy and chemotherapy schedules in limited small cell lung cancer: analysis of local chest recurrences☆

Abstract

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Role of radiation therapy in small cell anaplastic carcinoma of the lung

Cancer Treat. Rep.

Chemotherapy alone or chemotherapy with chest radiation therapy in limited stage small cell lung cancer: a prospective randomized trial

Ann. Intern. Med.

Is chest radiotherapy necessary in any or all patients with small cell carcinoma of the lung?

Yes. Cancer Treat. Rep.

Small cell lung cancer: Analysis of treatment factors contributing to prolonged survival

Cancer

Patterns of failure in small cell carcinoma of the lung

Cancer

Reassessment of loco-regional failure rate in relation with radiation dose in combined modality approach of multidrug chemotherapy and radiotherapy for limited-stage small-cell lung carcinoma

Interaction of thoracic irradiation and chemotherapy on local control and survival in small cell carcinoma of the lung

Cancer Treat. Rep.

Dose-time relationships and the local control of small cell carcinoma of the lung

Radiology

Importance of end points in determining effectiveness of thoracic irradiation for small cell lung carcinoma

The effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer. Initial results of a Canadian Multicenter randomized trial

Int. J. Radiat. Oncol. Biol. Phys.

Treatment of small cell lung cancer with VP-16, Vincristine, Doxorubicine (Adryamicine), Cyclophosphamide (EVAC), and high-dose chest radiotherapy

J. Clin. Oncol.