Population-based outcomes for small cell lung cancer: impact of standard management policies in British Columbia

Lung Cancer (2004) 43, 7—16

Population-based outcomes for small cell lung cancer: impact of standard management policies in British Columbia Janessa J. Laskin a,e,*, Sara C. Erridge b,e , Andrew J. Coldman c,e , Yulia D’yachkova c , Caroline Speers c , Virginie Westeel a , T. Greg Hislop c,e , Ivo A. Olivotto d,e , Nevin Murray a,e a

Division of Medical Oncology, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6 b Division of Radiation Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada c Division of Population and Preventive Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada d Division of Radiation Oncology, British Columbia Cancer Agency, Victoria, BC, Canada e The University of British Columbia, Victoria, BC, Canada Received 2 April 2003 ; received in revised form 30 June 2003; accepted 14 July 2003

KEYWORDS Small cell lung cancer; Population-based outcomes; Practice guidelines

Summary Survival data for small cell lung cancer (SCLC) is typically reported from clinical trials or institutional series that include patients fit enough to meet treatment criteria. The denominator of all SCLC patients from which the treated population is derived is rarely reported and the impact of new treatment strategies on population-based outcomes is difficult to measure. The British Columbia Cancer Agency (BCCA) is a single centralized agency that coordinates cancer treatment services in the province and develops and circulates province-wide treatment guidelines. All SCLC cases diagnosed in BC in 1990 and 1995 (n = 331 and 297, respectively) were identified. These 2 years were chosen specifically to examine the impact of a change in practice guidelines from consolidative to early concurrent thoracic radiation (RT) for patients with limited stage disease. Demographic, staging, treatment, and outcome details were obtained for 100% of cases. A total of 628 patients were reviewed, 207 with limited stage disease (LSCLC) and 407 with extensive stage disease (ESCLC); 14 cases diagnosed at post-mortem were excluded. Of the 207 patients with LSCLC disease, 170 (82%) received chemotherapy, and 138 (81%) of those that received chemotherapy also received thoracic radiation. A similar proportion (73 and 70%) of LSCLC patients received thoracic RT in both years but more patients in 1995 received early concurrent versus consolidative thoracic RT compared to those treated in 1990 (64% versus 17%, respectively, P = 0.001). Of the 407 patients with ESCLC, 71% received chemotherapy. The median overall survival for all patients was 7 months. Patients with LSCLC who received any chemotherapy had a median survival of 14.3 months (26.9 and 9.9% for 2- and 5-year survival, respectively). Patients with LSCLC who received chemotherapy plus thoracic RT had a median survival of 15.1

* Corresponding

author. E-mail address: [email protected] (J.J. Laskin). 0169-5002/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2003.07.004

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J.J. Laskin et al. months (32 and 12% for 2- and 5-year survival, respectively). Early concurrent thoracic RT in LSCLC was associated with an improved 5-year survival from 9.6 to 16.3% (P = 0.91). Patients with ESCLC who received any chemotherapy had a median survival of 8.4 months (7.3 and 2.3% for 2- and 5-year survival, respectively). Standard treatment guidelines generated population-based survival outcomes that are similar to published clinical trials. © 2003 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Lung cancer is notoriously difficult to treat and remains a significant cause of world-wide morbidity and mortality. Efforts to improve treatment modalities over the last 20 years have yielded little in the way of substantial improvements perhaps leading to a somewhat nihilistic approach to the treatment of lung cancer. This may also help to explain the variability of treatment approach and outcome world-wide [1—4]. Small cell lung cancer (SCLC) is a distinct pathologic entity representing approximately 15% of lung cancers in British Columbia (BC). Its unique natural history and response to therapy make diagnosis at an early stage essential for cure. With chemotherapy alone approximately 9% of patients with limited stage disease (LSCLC) will be long-term survivors [5,6]. This improves to 20—25% with integrated chemoradiation [7—13]. Patients with extensive stage disease (ESCLC) have a significantly worse outcome with only 1—2% surviving after 5 years [14—16]. A major objective of clinical trials is to identify interventions that can improve survival and be extrapolated into general clinical practice. The main sources of cancer survival statistics are institutional series or clinical trials and such patient populations are highly selected. Trials tend to be restrictive with respect to their eligibility criteria and in combination with possible referral biases and investigator screening biases this results in a better prognostic group of patients than could be expected in the general population of small cell lung cancer patients [17]. These selected populations may result in a potentially artificial set of treatment standards and outcome expectations. Population-based studies eliminate selection and referral bias. Such studies have looked at this issue in breast cancer [18], lung cancer, in general [2,19—21], and small cell lung cancer [15,22,23]. This study is a population-based review of the demographics, staging, treatment, follow-up, and survival for patients with SCLC in British Columbia diagnosed in 1990 and 1995. These years were chosen specifically to allow a minimum of 5 years of follow-up, and to evaluate the impact of changes

in treatment recommendations that occurred over that time [7—10,12].

2. Patients and methods 2.1. Setting The province of British Columbia is 450,000 km2 and has a population of 4 million. The British Columbia Cancer Agency (BCCA) has the mandate for cancer control in the province including the maintenance of the BC Cancer Registry, operation of cancer screening programs, provision of all radiation therapy (RT) and management of the budget for all antineoplastic drugs. Currently, the agency has four geographical sites within the province. No private radiotherapy facilities exist in British Columbia and therefore all radiation therapy is delivered at one of the four BCCA centers. Chemotherapy is generally coordinated through the BCCA, but may be given by a physician in the community. Comprehensive universal health care ensures that treatment is not restricted for financial reasons. The centralized nature of the BCCA allows for consensus statements and treatment recommendations to be circulated to all physicians who treat cancer in British Columbia. These evidence-based guidelines are generated by a multi-disciplinary panel of experts in the field and are reviewed and updated regularly. They are available on-line (http://www.bccancer.bc.ca); prior to 1997 a printed copy was distributed regularly.

2.2. Data sources The BC Cancer Registry was used to identify all cases of SCLC diagnosed in British Columbia in 1990 and 1995 (n = 628). The BC Cancer Registry has a 93.5% case completeness ascertainment rate (according to the North American Association of Central Cancer Registries). The data are entered prospectively and updated regularly. For cases referred to the BCCA (458/628; 73%) BCCA charts were used to retrospectively record demographic, pathology, staging investigation, treatment and outcome information. For cases not referred to the BCCA, similar data for each

Population-based outcomes for small cell lung cancer patient was obtained from primary physicians through surveys or up to three telephone contacts. A full dataset was complied for 100% of cases. Distance (≤2 or >2 h drive) from the patients’ residence at diagnosis to the nearest BCCA site was recorded. Information on performance status was not uniformly recorded in the database and it was felt to be inappropriate to assign this retrospectively. Survival data was updated in October 2002.

2.3. Staging and diagnostic procedures Patients were classified according to the Veteran’s Administration Lung Cancer Study Group [24] as having limited (confined to one hemithorax including hilar, ipsilateral and contralateral mediastinal, and ipsilateral and contralateral supraclavicular lymph nodes) or extensive stage disease (includes patients with malignant pleural effusion). The physician(s) primarily looking after the patients assigned the stage of the cancer. Screening recommendations for extrathoracic metastatic disease did not change from 1990 to 1995. Baseline screening included: standard serum chemistry including liver function tests and transaminases, LDH, creatinine, calcium and CEA. A chest X-ray was recommended for everyone but a CT scan of the chest was left to the discretion of the treating physician. It was recommend that all patients receive imaging of the upper abdomen to include the liver and adrenal glands with either CT or ultrasound. A CT of the brain was also recommended. Bone scans or bone marrow aspirates and biopsies were not suggested as routine investigations unless patients displayed suspicious signs or symptoms. Once extensive stage disease was detected, it was not always deemed necessary to complete the roster of diagnostic procedures. All patients were required to have had a pathological or cytological diagnosis of SCLC. Information was also collected on the type(s) of chemotherapy used, and the sites, dose and timing of radiation therapy. For patients not receiving chemotherapy or RT, any reasons were recorded from chart notes or statements from the primary physician.

2.4. Treatment recommendations In accordance with the BCCA guidelines, in 1990 and 1995, patients with limited stage disease were offered four to six cycles of combination chemotherapy and thoracic radiation therapy [25,26]. The policy in 1990 was to deliver RT following chemotherapy. As a result of trials demonstrating a survival benefit for early concurrent thoracic RT [7—10,12]

9 BCCA treatment recommendations were changed in 1993 to include the administration of thoracic RT concurrently with etoposide and cisplatin within the first 6 weeks of chemotherapy. In both 1990 and 1995, prophylactic cranial irradiation was recommended for LSCLC patients with a complete response to chemoradiation. In both years the BCCA treatment recommendations for patients with extensive stage disease were to offer combination chemotherapy for those deemed fit enough to receive it. Patients who were less fit may have received either combination or single agent chemotherapy, palliative radiation or symptomatic management alone. A few patients with small bulk ESCLC obtained a complete response to chemotherapy and were offered prophylactic cranial radiation [27].

3. Analysis Descriptive statistics were used for most comparisons. Proportions of patients receiving treatments by various disease or treatment characteristics were compared using the chi-square test. Survival probability was estimated with the Kaplan—Meier method and compared (between 1990 and 1995 and different diagnostic and treatment modalities) using the Log-Rank test. Survival status and cause of death was updated in October 2002 using the division of Vital Statistics database.

4. Results A complete dataset was obtained for all of the 628 patients diagnosed with SCLC in British Columbia in 1990 and 1995 (331 and 297 cases, respectively). Fourteen cases diagnosed post-mortem were excluded from the analysis. Demographic information on the remaining 614 patients is detailed in Table 1. The gender (55% male), age distribution (median age = 68 years) and proportion of patients with limited stage disease (34%) was similar between the 2 years. Information was available on the following tests used for staging purposes: Chest X-ray, CT or ultrasound of the abdomen, bone scan and brain scan (CT). All subjects received chest X-rays. As expected, the use of individual tests varied with the extent of disease (Table 2). Similar proportions of each disease subgroup received abdominal scans (78% versus 81%); whereas limited stage patients were more likely to receive bone scans (71% versus 56%, P < 0.001) and brain scans (66% versus 57%, P = 0.033) than patients with extensive

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J.J. Laskin et al.

Table 1 Patient characteristics Characteristics

Age (years) <60 60—70 70—80 >80 Median Gender Male Female

All Patients

LSCLC

N = 614

%

138 226 202 48

23 37 33 8

67.5

N = 207 44 74 74 15

ESCLC %

N = 407

%

21 36 36 7

94 152 128 33

23 37 32 8

68.8

340 274

55 45

disease. Use of the various staging tests did not vary between 1990 and 1995. Just over half (54%) of limited stage cases had all tests performed and 12% had a chest X-ray only. The median overall survival for all 614 patients was 7 months (95% confidence interval from 6.7 to 8.5 months), with a 2-year survival of 11.4% and 5-year survival of 3.9%. The median disease specific survival was 7.8 months. Overall survival for 1990 and 1995 were not significantly different at (P = 0.58) with median survivals of 7.8 and 7.6 months, respectively. The overall survival by stage is shown in Fig. 1. Among the 456 patients who received initial chemotherapy, 50% started within 2 weeks of diagnosis, 70, 82, 89 and 92% were started by 3, 4, 5 and 6 weeks, respectively.

4.1. Limited stage SCLC There were 207 (34%) patients with limited stage disease, 113 in 1990 and 94 in 1995. Of these,

113 94

66.8 55 45

227 180

56 44

170 (82%) received chemotherapy and 138 (81% of the 170) received both chemotherapy and thoracic radiation. Chemotherapy was primarily cisplatin-based. A treatment summary is outlined in Table 3. In 1990, 92 (81%) patients with limited stage disease received chemotherapy and of these 76 (83%) received combined modality therapy. In 1995, 78 (83%) patients were treated with chemotherapy and 62 (78%) patients received combined therapy. In 1995, 63% (39/61) of patients received early radiation therapy (defined as thoracic radiation given within 6 weeks of the start of chemotherapy) compared with 17% (13/76) in 1990 (P = 0.001) (Table 3). Survival of patients with LSCLC was examined according to the timing of thoracic radiation (Table 4). Although median survival was similar in both groups, early concurrent therapy was associated with a trend towards a better 5-year survival rate of 16.3% compared to 9.6%, this difference was not statistically significant (P = 0.91).

Table 2 Use of imaging tests by extent of disease and year of diagnosisa Tests

1990 LSCLC (N = 113) (%)

1995 LSCLC (N = 94) (%)

1990 ESCLC (N = 206) (%)

1995 ESCLC (N = 201) (%)

CXR only CXR plus abdominal imaging CXR plus abdominal imaging plus CT head CXR plus abdominal imaging plus bone scan

13 (12) 90 (80)

11 (12) 72 (77)

12 (6) 169 (82)

15 (7) 160 (80)

69 (61)

53 (56)

97 (47)

99 (49)

13 (12)

8 (9)

23 (11)

24 (12)

All four tests

63 (56)

49 (52)

72 (35)

73 (36)

a

Information on the following tests was available: Chest x-ray (CXR), abdominal ultrasound or CT, bone scan and CT head.

Population-based outcomes for small cell lung cancer

11

1.0

Survival Probability

.8

.6

.4

.2

Limited Extensive

0.0 0

1

2

3

4

5

6

7

Time (years since diagnosis) Fig. 1

Overall survival for limited and extensive stage SCLC.

Table 3 Overall therapy given to patients with limited and extensive stage disease divided by year Therapy

1990 LSCLC (N = 113) (%)

1995 LSCLC (N = 94) (%)

1990 ESCLC (N = 206) (%)

1995 ESCLC (N = 201) (%)

Any therapy Any chemotherapy

99 (88) 92 (81)

82 (87) 78 (83)

163 (79) 147 (71)

151 (75) 141 (70)

Initial chemotherapy regimen CAV or EP CAV alternating with EP CODE/PAVE Oral etoposide Other combination Second line chemotherapy Any thoracic RT Chemotherapy plus thoracic RT

23 (20) 41 (36) 10 (8) 4 (4) 14(13) 22 (19) 83 (73) 76 (83)

8 34 18 13 4 6 66 61

Dose initial thoracic XRT (Gy) 1500—2999 3000—3999 ≥4000

33 (27) 24 (21) 26 (23)*

9 (9) 18 (19) 39 (42)*

42 (20) 10 (5) 3 (2)

Thoracic XRT ≤6 weeks of initial chemotherapy 6—24 weeks of initial chemotherapy Prophylactic CNS XRT RT to sites other than chest or CNS

13/76 (17)** 58/76 (76) 41(36) 20 (18)

39/61 (64)** 21/61 (34) 27 (28) 19 (20)

6 35 19 50

(9) (36) (19) (14) (4) (6) (70) (78)

49 30 28 10 30 24 58 45

(24) (15) (14) (5) (15) (12) (28) (22)

(3) (17) (9) (24)

28 26 54 27 5 24 67 60

(14) (13) (27) (13) (2) (12) (33) (30)

112 (18) 75 (12) 80 (13) 23 29 16 48

(11) (14) (8) (24)

CAV: cyclophosphamide, doxorubicin and vincristine; EP: etoposide, cisplatin; CAV/EP alternating regimen; CODE: weekly cisplatin, doxorubicin, vincristine, etoposide; PAVE: q3 weekly cisplatin, doxorubicin, vincristine, etoposide; RT: radiation therapy. * P ≤ 0.001. ** P = 0.001.

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J.J. Laskin et al.

Table 4 Survival by stage and therapy received Group

Total (%)

Median (months)

2-year (%)

5-year (%)

All LSCLC ESCLC Received any CT ESCLC–—received any CT LSCLC–—received any CT LSCLC–—any CT and thoracic RT

614 207 407 458/614 288/407 170/207 138/170

(75) (71) (82) (81)

7.7 12 5.6 10.4 8.4 14.3 15.1

11.4 23 5.4 14.7 7.3 26.9 32

4.0 8 1.8 5 2.3 10 12

52/138 (38) 85/138 (62)

14.4 15.1

30.4 32.9

16.3* 9.6*

LSCLC TRT start ≤6 weeks of CT start TRT start >6 weeks of CT start

TRT: thoracic radiation therapy; CT: chemotherapy. * P=0.91.

no difference in survival between 1990 and 1995 (P = 0.62) (Fig. 2). Significantly more patients in 1995 received greater than or equal to 40 Gy of thoracic radiation compared to patients in 1990 (P = 0.007; Table 3). Thirty-six percent of patients with LSCLC in 1990 and 28% in 1995 received prophylactic cranial irradiation.

In a non-integrated treatment regimen patients had to have lived long enough to receive consolidative radiation therapy. Therefore, a subgroup analysis for survival was done on patients with LSCLC who lived for more than 12 weeks after diagnosis. As 8 out of 138 patients who received both chemotherapy and thoracic radiation died within 12 weeks, 130 patients were analyzed. By definition early integrated radiation therapy for LSCLC had to start within 6 weeks of chemotherapy. Thoracic radiation was planned to coincide with the second cycle of chemotherapy. There was no significant difference in survival of patients receiving and not receiving early integrated radiation therapy (P = 0.82) and

4.2. Extensive stage SCLC Table 3 outlines the therapy received by the 407 patients with extensive stage disease. There were no significant differences between 1990 and 1995

1.0

Survival Probability

.8

.6

.4

Dx 1995 .2

Dx 1990 0.0 0

1

2

3

4

5

6

7

Time (years since diagnosis) Fig. 2

Survival of patients with LSCLC who survived at least 12 weeks, separated by year (P = 0.62).

Population-based outcomes for small cell lung cancer

13

in the proportion receiving any chemotherapy (71%) any thoracic RT (31%), prophylactic cranial RT (9%) or RT to other sites (24%). Survival figures for patients with ESCLC are outlined in Table 4. The median survival for all 407 patients was 5.6 months with 2- and 5-year survival rates of 5.4 and 1.8%, respectively. Patients who received any chemotherapy had an improved median survival to 8.4 months, this was not statistically significant. The survival outcomes remained unchanged between 1990 and 1995.

ferred to the BCCA than those who lived within two hours (P < 0.001). The differences in rates of BCCA referral were smaller for patients with limited stage (88% versus 77%, P = 0.04) than extensive stage disease (77% versus 50%,s P < 0.001). There were no differences in the likelihood of receiving chemotherapy and/or radiation therapy based on proximity to a cancer centre (Table 6). The overall survival did not vary with patient’s location (P = 0.9).

4.3. Patients who did not receive treatment

5. Discussion

There were 158 (26%) patients who did not receive any chemotherapy (18% with LSCLC and 29% with ESCLC). Reasons are outlined in Table 5 and include: patient refusal (51), poor physical condition (47), contraindication (12), and other (31). Advanced age was the principal reason for not receiving chemotherapy in only eight cases. Three hundred and forty patients did not receive radiation therapy primarily because treating physicians felt it was not required.

Data from this population-based SCLC analysis serve several purposes: it describes the demographic, staging, treatment and outcome characteristics of a population of patients with SCLC in a geographically defined area; it compares the outcomes in this population to the results of clinical trials; and it assesses the impact of practice guideline changes on patterns of practice and survival. Patient characteristics such as age, gender and stage in our study group are similar to those reported in other population-based series [15,22,23]. There was little difference in the staging investigations done in 1990 and 1995 likely because there was no change in the BCCA recommendations. It is notable that only half of the patients with limited stage disease had the complete set of imaging tests recommended and thus it is certainly

4.4. Differences by location of residence One hundred and sixty-seven patients (27%) lived in ‘‘remote’’ locations, defined as more than a two-hour drive from one of the regional cancer centers. These patients were less likely to be re-

Table 5 Reasons patients did not receive chemotherapy or initial thoracic radiation therapy Reason Chemotherapy Patient declined Poor physical condition Contraindication Advanced age Other or unknown Total not receiving chemotherapy Radiation Patient declined Poor response or chemotoxicity Poor physical condition RT not required Contraindication Advanced age Other or unknown Total not receiving RT RT: Radiation therapy.

1990 LSCLC (n = 113)

1995 LSCLC (n = 94)

1990 ESCLC (n = 206)

1995 ESCLC (n = 201)

7 7 1 2 4

8 3 3 0 3

14 22 2 3 18

22 15 6 3 15

21

17

59

61

7 2 6 6 1 0 8

6 4 6 6 1 0 5

12 5 10 92 4 2 23

16 12 17 72 3 1 13

30

28

148

134

14

J.J. Laskin et al.

Table 6 Referral and treatment by distance from

patients residence (close versus remote defined as taking more than 2 h to drive to a cancer centre) Close (≤2 h drive) (%)

Remote (>2 h drive) (%)

1990–—patients referred LSCLC 69 (89) ESCLC 115 (75)

31 (87) 30 (57)

1995–—patients referred LSCLC 57 (88) ESCLC 119 (79)

18 (62) 21 (42)

Chemotherapy LSCLC 115 (80) ESCLC 212 (70)

55 (86) 76 (74)

Thoracic RT LSCLC ESCLC

103/143 (72) 97/304 (32)

46/64 (72) 28/103 (27)

Any RT LSCLC ESCLC

112/143 (78) 159/304 (52)

48/64 (75) 42/103 (41)

LSCLC: limited stage small cell lung cancer; ESCLC: extensive stage small cell lung cancer; RT: radiation therapy.

possible that a number of these patients truly had extensive disease. This rate of investigations is less than expected in a clinical trial setting but is similar to other population-based studies of SCLC [2,23] except that Lebitasy et al report a higher rate of brain scans, approximately 86%, in a similar time period. Cottin et al. report that only 31% of 57 patients not involved in a clinical trial underwent all recommended staging investigations [17]. There was some year to year variation in the specific combination chemotherapy regimens delivered; this reflects ongoing clinical trials and a shift in patterns of practice. For example, in 1995 more patients received CAV alternating with EP because early integrated radiation therapy was given concurrently with the EP whereas in 1990 more patients were offered CAV with consolidative radiotherapy. In this geographically defined unselected population 2- and 5-year survival rates of 11.4% and 3.9% and median survival of 7.7 months were similar to that of published clinical trials. Patients with limited stage disease enrolled in clinical trials have reported median survivals of 9.9—17.7 months [16] which is comparable to our results of 12—15 months for limited stage patients receiving combined modality treatment. Likewise, a meta-analysis by Pignon et al. [5] reported 3-year survivals of 8.9—14.3% for patients with LSCLC;

these figures are comparable to the 14.1% 3-year survival in the current study. Outcomes for patients with ESCLC enrolled in North American trials over the last 30 years have been summarized [14,16]. Albain reported median survivals of 6.9 to 11.5 months. Chute et al. [14] reported a median survival of 7.6 months for patients on the control arms of several Phase III trials. These results are comparable to the median survival of 8.4 months for patients who received any chemotherapy in this population-based cohort. In a geographically large province, such as British Columbia, it is appropriate to be concerned about the efficacy and effectiveness of delivering equal health care opportunities. The fact that there was no relationship between the distance to a cancer centre, treatment delivery and survival is reassuring, particularly with respect to radiation therapy which can only be delivered at a cancer centre. The centralized nature of the British Columbia Cancer Agency promotes the development and the wide distribution of evidence-based practice guidelines designed to help physicians identify and apply state-of-the-art treatment regimens. Although in the 2 years we examined, only 81% of the entire population of patients who presented with SCLC received any chemotherapy or radiation, outcomes are similar to those seen in clinical trials. This supports the idea that standardized treatment recommendations may not encompass the entire population; however, in comparison to other population-based studies this is a high rate of therapeutic adherence [15,19,21,22,28]. Importantly, shifts in BCCA evidence-based practice guidelines led to a change in province-wide pattern of practice. Although we have data from only two non-consecutive years, we observed a shift in 1993 from consolidative thoracic irradiation to early concurrent chemoradiotherapy for LSCLC. Implementing this change required a change in referral practice so patients would see a radiation oncologist as early as possible after diagnosis. This study demonstrates a significant increase in the proportion of LSCLC patients receiving early thoracic RT, consistent with the recommended guidelines. Patients with LSCLC who received thoracic radiation therapy within 6 weeks of chemotherapy had an improvement in 5-year overall survival rates from 9.6 to 16.3% though this was not a statistically significant difference. Despite the evolution of patterns of practice it is difficult to demonstrate a significant gain in survival in this population. This is related to the small number of patients with SCLC in the population, compliance to recommendations, and perhaps most importantly, the overall limited magnitude of treatment

Population-based outcomes for small cell lung cancer

15

Table 7 Comparison of population-based outcome results for patients with small cell lung cancer Era

N

Received CT (%)

Received RT (%)

OS or MS

Janssen-Heijnen et al. [22]

1974—1994

1796

36—5

OS: 8% 2 years

Lebitasy et al. [23] Gregor et al. [19]

1981—1994 1995

787 678

30—82 (<70 years); 15—56 (>70 years) 76—91 63

53—25 LSCLC–—23

Davis et al. [15]

1974—1982

1538

69

56

MS: 6.6—11 months All MS: 3.7 months; LSCLC: 5.6 months; ESCLC: 2.1 months OS: LSCLC–—35% 2 years; OS: ESCLC– —3% 2 years

Laskin, current study

1990 and 1995

614

75

45

LSCLC

207

82

72

ESCLC

407

71

31

LSCLC–—OS: 23% 2 years; MS: 12—15 ESCLC–—OS: 5.4% 2; MS: 6—8

CT: chemotherapy; RT: radiation therapy; SCLC: small cell lung cancer; NSCLC: non-small cell lung cancer; LSCLC: limited stage small cell lung cancer; ESCLC: extensive stage small cell lung cancer; OS: overall survival in years; MS: median survival in months.

effect that necessitates large numbers of patients to show a statistical difference in survival outcome. Population-based studies are useful to evaluate the applicability and impact of clinical trials in clinical practice. In recent years, there have been a number of population-based studies demonstrating considerable variability in standard treatment and survival rates for patients with lung cancer [1,2,19,20,29]. These studies have helped describe patient characteristics, treatment, and survival in general populations. There have been four population-based reports for lung cancer, in general [2,19—21], and three for small cell lung cancer specifically [15,22,23], these are outlined in Table 7. The current study is at least comparable to these studies particularly with respect to overall survival and to the delivery of chemotherapy. This may, at least in part, be due to our readily available practice guidelines. In this era of evidence-based medicine, therapeutic modalities are evaluated within a paradigm in which clinical trial outcomes are extrapolated from a select group to the population as a whole. While the logic of this approach is appropriate, it is essential to be able to evaluate how applicable the results are to the population as a whole. Rarely do clinical trials provide an estimate of the number of patients for which a given therapy may be appropriate, or the denominator of applicability. One must also consider the absolute size of improvement and the degree to which the magnitude of change will

be diffused throughout the population. Given that we were able to treat only 22% of all patients with combined modality therapy with curative intent, a realistic estimate of the impact of therapeutic innovations must consider these population-based realities.

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[19]

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[23]

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