226 Abstracts/Lung Cancer 13 (1995) 185-232

Radiotherapy

Increased radioresistance of an in vitro transformed human small cell lung cancer cell line Brodin 0, Arnberg H, Bergh J, Nilsson S. Dept. of Oncology. Akademiska Hospital, Uppsala iJniversi&, Uppsala S-751 85. Lung Cancer (Ireland) 1995; 12: 183-98.

Alter 4-6 months in continuous culture the human small cell lung cancer (SCLC) cell line, U-1906, changed its radiobiological character- istics spontaneonsly. The cell linebecame more radioresistant indicating an increased repair capacity. This change was accompanied by a more adherent growth pattern, a higher clonogeneity, a decrease in the cytokexatin (tissue polypeptide antigen) content and increased ghrcagon and neuron-specific enolase (NSE) production. Other parameters such as the estramustine-binding protein (EMEP) and the proliferation associated antigen Ki-67 were unaltered. This spontaneous transformation in vitro of U-1906 may reflect a clinically important in viva phenomenon of SCLC, which frequently develops resistance both to radio- and chemotherapy.

New therapeutic strategies involving radiation therapy for patients with non-small cell lung cancer Curran WJ Jr. Department of Radiation Oncologv Thomas Jefferson CJniversi@, Philadelphia. PA. Chest 1995;107:6 Suppl:302S-5s.

Recent notable developments have occurred involving radiation therapy (RT) for patients with non-small cell lung cancer (NSCLC). For patients with good performance status with tutresected thoracic tumors, induction cisplatin- based chemotherapy followed by RT has resulted in a significant survival advantage over RT alone in two North American trials. However, the best sequence of administration of these two modalities in NSCLC remains to be determined. For palliation of tumor-related symptoms, efforts under way to improve control of brain metastams include the use of twice-daily cranial RT to a higher total dose, the use of focused radiation boost techniques like stereotactic radiosurgery to small metastatic deposits, and increased use of neurosurgical extirpation. For patients with NSCLC with symptomatic bone metastases, use of wider-field irradiation may benefit selected patients. Memstases to the adrenal gland, liver, and s&cutaneous tissues can be palliated successtitlly by brief coorses of RT. Intrathoracic tumor symptoms are well palliated by brief courses of thoracic RT. As adjuvant therapy following curative surgery, RT reduces the intrathoracic tumor recurrence rate among patients with metastatic tumor foci in hilar or mediastinal lymph nodes.

Thoracic and cranial radiotherapy for limited-stage small cell lung cancer Healey EA, Abner A. 50 Binney St, Boston, MA 02I55. Chest 1995;107:Suppl:249S-254s.

Chemotherapy remains the mainstay of treatment for small cell lung cancer (SCLC). For patients with limited-stage disease, the addition of thoracic radiotherapy confers a moderate improvement in local control and a modest survival benefit, but these improvements come at the cost of increased toxic reactions. The optimal method for integrating chemotherapy and thoracic radiotherapy is unresolved. Concurrent and alternating strategies are appealing because they allow uninterrnpted delivery of chemotherapy, but they have not been proven to be superior to conventional sequential approaches. Based on limited data, delivery of thoracic radiation early in the treatment course may be preferable to delivery later in the conme. There is evidence ofa radiation dose-response

effect for SCLC, and, in standard regimens, thoracic radiation doses in the range of 50 to 60 Gy are recommended. The nse of limited radiation fields (to postchemotherapy tumor volumes) appears reasonable. Results for alternative thoracic radiation fractionation schedules such as accelerated hyperfractionation are promising and worthy of further investigation. The role of prophylactic cranial irradiation (XI) is controversial and should be individualized. It should be considered for the favorabk SU&WqI ofpatients witb hnited-stage discaae who achieve a complete response to chemothetapy and thoracic radiothetapy, Ifgiven, we recommend a total dose of30 to 36 Gy in 2-Gy fraction; PC1 should not be delivered concomitantly with chemotherapy.

Initial report on the effectiveness of high dose rate brachytherapy in the treatment of hemoptysis in lung cancer Sur RK, Mahomed GA, Pacella JA, Levitt VC, Feldman C, Donde B. Department of Radiation OncoIogv Hillbrow Hospital, Private Bag 23140, Joubert Park, Johannesburg 2044. Endocuriether Hyperthermia Gncol 1995;11:101-6.

Fourteen patients with advanced and recurrent lung cancers following a radical course of external beam radiotherapy three to 18 months (mean, ten months) previously were treated with a single fraction of high dose rate intraluminal brachytherapy of 10 Gy for severe uncontrolled hemoptysis. Following treatment, hemoptysis decreased within ten to 24 hours (mean, 15.3 hours) and stopped completely within 72 hours in 13 patients. lkvelve of these 14 patients had no further recurrence of hemoptysis three to nine months following treatment. One patient whose hemoptysis decreased initially died three months later of massive uncontrolled hemoptysis. This hemoptysis was not controlled with a second fraction of 10 Gy. The other patient had recurrent hemoptysis two months after the first brachytherapy treatment. This was treated with a further 10 Gy following which the hemoptysis stopped, and the patient is alive two months after the second treatment. High dose rate intraluminal brachflerapy is effective for the treatment of uncontrolled hemoptysis from recurrent or residual tnmor following a course of radical external beam radiotherapy.

Radiotherapy in non-small cell lung cancer: Optimal doses and schedules Schaake-Koning C. The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis. Plesmanlaan 121, 1066CX Amsterdam. Lung Cancer (Ireland) 1995;12 Suppl l:S119-23.

The doses and schedules for radiation therapy as applied in Stages IIlB and IIIA non-small cell lung cancer patients show a great variety. Depending on its intent, several purely palliative schemes can be used. When a curative intent scheme is wnsidered, patients can lx treated with a more experimental approach as several options are tested to increase selectively the radiation dose in the tumour areas. If improvements in treatment schemes are proven, new standards can be set.

Radiotherapeutic management of non-small cell lung cancer (NSCLC): An overview based on the clinical trials of the Radiation Therapy Oncology Group (RTOG) Wilson JF, Byhardt RW. Department of Radiation Oncology, Medical College of Ksconsin, 8700 West Wisconsin Avenue, Milwaukee, WI 53226. J Jastro 1995;7: l-10.

Recent clinical trials clarified the role of radiation therapy (RT) in the treatment of non-small cell lung cancer (NSCLC). The evolution of this research is illustrated by a systematic succession of studies conducted

Abstracts/Lung Cancer 13 (1995) 185-232 221

during the last twenty years by the Radiation Therapy Oncology Group @TOG). Initial studies demonstrated the dependence of local tumor control and survival on total dose of standard fractionation RT for unresectable NSCLC. Subsequent studies evaluated radiation dose intensification, employing altered fractionation RT administered as either hyperfractionated or accelerated fractionation RT. Altered fractionation schemes achieved total doses as much as 32% higher than standard RT to 60 Gy, which necessitated careful reassessment of acute and late treatment-related toxicity, These studies showed a survival advantage for hyperfractionation to 69.6 Gy, in favorable performance patients, compared to hyperfractionation to 60 Gy. Current dose intensification investigations include evaluation of 3-dimensionaU confonnal RT as a means of delivering high doses of standard Iiactionation RT with low toxicity. Treatment intensification utilizing combined chemotherapy (CT) and RT for NSCLC has also been evaluated. Recent studies have demonstrated improved local control and survival with induction CT followed by standard RT to 60 Gy. Current studies will evahiate the timing and sequencing of CT and RT and the combination of CT with altered fractionation RT. Hypoxic cell sensitizers and nonspecific immune stimulants, two noncytotoxic adjwants to RT, have shown no survival be&it. Biologic response modiflers, including recombinant interferon-beta, will also be evaluated as adjuvants to standard RT, based on interferon-beta radiosensitization observed in the laboratory and clinical investigations suggesting improved survival. Overall, RTGG studies have yielded small, but @artant, incremental improvements in treatment outcome for NSCLC, enhanced understanding of the pathophysiology of NSCLC, and provide a solid foundation on which to develop tiuure investigations.

Single fraction prophylactic cranial irradiation for small cell carcinoma of the lung Brewster AE, Hopwood P, Stout R, Burt PA, Thatcher N. Manchester Lung Tumour Gtwup. Department of Radiotherapy, Christie Hospital, Manchester A420 4BX. Radiother Oncol 1995;34:132-6.

The effectiveness of a single 8-Gy fraction prophylactic cranial irradiation regime was assessed in 106 patients with small-cell carci- noma of the lung. .All patients had limited stage disease and received combination chemotherapy consisting of either cisplatin or carboplatin with ifosfamide, etoposide, and vincristine (VICE). Cranial irradiation was administered 48 h after the first cycle of chemotherapy and was well tolerated. Actual Z-year survival was 35% and cranial relapse occurred in 22% of those patients who achieved complete remission. This compares favourably with a cranial relapse rate of 45% incomplete remitters previously reported with the same chemotherapy regime after a minimum follow-up of 2 years where PC1 was not used. Formal psychometric testing was performed retrospectively on a series of 25 long-term survivors of whom 14 were taken from this reported series. Whilst 75% of patients were impaired on at least one test with 68% performing badly in the most complex task, this was not associated with clinically detectable neurological damage and the patients did not complain of memory or concentration difficulties, In conclusion, single fraction PCI, when used with platinum based combination: chemo- therapy, appears tobe equally effective but may be less neurotoxic than the more standard fractionated regimes.

Factors causing radiation pneumonitis and the CT findings in lung cancer cases Sanka Y Department ofRadiology, Osaka Medical College, Osaka 569. Jpn J Lung Cancer 1995;35:7-15.

By using chest CT, we investigated the factors and CT findings of

radiation pneumonitis. In 70 cases which were treated by radiotherapy with a total dose of over 30 Gy and followed up over 2 months after radiotherapy, radiation pneumonitis was detected in 49 cases (70.0%). There was no signitIcant correlation between the occurrence Of radiatiOn

pneumonitis and the size of the radiation field. Combined chemotherapy was not related to the occurrence of radiation pneumonitis. However, there was a higher incidence of radiation pneumonitis in cases with over 4 courses of chemotherapy. In 25 cases with diffuse lung disease, radiation pneumonitis was detected in 22 cases (88.00%) and extended beyond the radiation field in I2 cases. Diffuse lung disease had significant intluence on the occurrence of radiation pneumonitis. We found various CT findings of radiation pneumonitis, including ground glass appearance, patchy, reticular, honeycomb and subpleural increased density. We investigated the clinical usefulness of 3-D imaging using helical scan CT. 3-D CT imaging was useful to observe the extent of radiation pneumonitis and to follow changes in CT findings.

Combined treatment modalities

The combined treatment with surgery and chemotherapy: Primary approach to small cell lung carcinoma (SCLC) Cui S, Li H, Gu Y Department of Thoracic Surgery, Henan Pmvincial Hospital, Zhengzhou 450003. Chin J Oncol 1994;16:432-4.

Forty cases of small cell lung carcinoma (SCLC) treated with surgical and chemotherapeutic combined therapy were reported. There were 28 males and I2 females in the group, most with history of more than 2 months, ranging in age of 27 - 66 years old. Cough, bloody sputum, low fever and chest distress are the main clinical manifestation. The small cell undifferentiates carcinoma was contirmed by tiberbron- choscope examination and pathology in all patients. Single lobectomy was performed in 20 cases, lobectomy of the upper and middle lobe in 9 cases, (sleeve resection of the lobarbronchus in 3 cases), and total pneumonectomy in 7 cases. Iwo cases were of stage I, I8 were of stage II, and 20 were of stage III a. Twelve patients received chemotherapy after operation, and 28 patients underwent the ‘chemotherapy -operation - chemotherapy’ treatment model. Adriamycin (or CDDP), cytoxan, vincristin, and dexamethasone were used for the chemotherapy procedure. The I, 3,5-year survival rate of chemotherapy after operation and chemotherapy - operation - chemotherapy group were 70%. 45%, 30.5% and 54% 30% and 22%. respectively. It is demonstrated that the long-term survival rate could be elevated in SCLC patients treated with chemotherapy after surgical operation, and the chance of operation also could be elevated by preoperative chemotherapy. The resection rate was 93% in the preoperative chemotherapy group.

Immunotherapy with the use of tumor-infiltrating lymphocytes and interkukin-2 as adjuvant treatment in stage III non-small- cell lung cancer: A pilot study Ratto GB, Melioli G, Zino P, Mereu C, Mirabelli S, Fantino G et al. Istihrto Patologia Chirqica, Universily of Genoa, Male Benedetto XK 16132 Genova. J Thorac Cardiovasc Surg 1995;109:1212-7.

This study assesses the feasibility and toxicity of adoptive immuno- therapy with tumor infiltrating lymphocytes and recombinant interleukin-2 in 29 patients underwent resection for stage III non-small- cell lung cancer. In five patients cultures yielded no growth of tumor infiltrating lymphocytes. In the remaining patients (stage IIIa, 14 cases; stage IIIb, IO cases) tumor infiltrating lymphocytes were in vitro expanded from surgically obtained tissue samples, including samples from both the tumor and surrounding lung. A number of tumor