Prophylactic Cranial Irradiation for Patients with Small-Cell Lung Cancer in Complete Remission

Aupérin, Anne; Arriagada, R.; Pignon, Jean-Pierre; C, Le Péchoux; Gregor, A.; Rj, Stephens; Pe, Kristjansen; Be, J.; Ueoka, Hiroshi; Wagner, Henry; Aisner, Joseph

doi:10.1056/nejm199908123410703

Cited by 1,559 publications

(1,001 citation statements)

References 29 publications

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“…The second approach is, in fact, a new study taking into account all performed studies on the topic, published or not, requiring individual data updated by the investigators and is much more time-consuming. Nevertheless, our approach based on the literature provides similar results as shown by our meta-analysis on the role of prophylactic cerebral irradiation in small-cell lung cancer , where the results based on published data were the same as those found in the meta-analysis based on individual patients data (Auperin et al, 1999).…”

Section: Discussionsupporting

confidence: 75%

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

et al. 2004

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Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30 -1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.

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Section: Discussionsupporting

confidence: 75%

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

et al. 2004

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“…meta-analysis on the role of prophylactic cerebral irradiation in small-cell lung cancer , based on published data, we obtained the same results as in the meta-analysis based on individual data (Auperin et al, 1999). Variations in survival results among the studies could be explained by the heterogeneity in methodologies used to stain and count microvessels in the tumours in addition to variation in patients population.…”

Section: Discussionsupporting

confidence: 63%

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

et al. 2002

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In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a metaanalysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16 -2.84), CD34 (HR: 1.99; 95% CI: 1.53 -2.58) or CD31 (HR: 1.80; 95% CI: 1.10 -2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.

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“…The use of PCI significantly reduced the obvious development of brain metastases at one year 7.7% vs. 18% for PCI vs. observation without improved overall survival benefit reported by RTOG 0214 phase III non‐small‐cell lung cancer study (2) . For limited stage small‐cell lung cancer, three years' overall survival improved from 14% to 21%, and decreased incidence of brain metastases from 59% to 33% due to PCI (3) . Similarly, the use of PCI for extensive stage small‐cell lung cancer has shown three years' overall survival improved from 13% to 27% and reduced incidence of brain metastases from 40% to 15% at one year (4) .…”

Section: Introductionmentioning

confidence: 93%

“…Whole‐brain radiotherapy (WBRT) is a common treatment modality in patients with multiple brain metastases, (1) given as prophylactic cranial irradiation (PCI) for non‐small‐cell (2) /small‐cell lung cancer, 3 , 4 and cranial and craniospinal irradiation for pediatric/adult central nervous system malignancies 5 , 6 . For solitary brain metastasis postoperatively, WBRT reduced intracranial failure from 70% to 18%, an absolute gain of 52% in any brain failure compared to without WBRT (1) .…”

Section: Introductionmentioning

confidence: 99%

Potential for reduced radiation‐induced toxicity using intensity‐modulated arc therapy for whole‐brain radiotherapy with hippocampal sparing

Pokhrel

Sood

Lominska

et al. 2015

J Applied Clin Med Phys

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The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity‐modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole‐brain radiotherapy (NC‐WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1‐weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole‐brain planning target volume (WB‐PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high‐definition multileaf collimators (HD‐MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam‐on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB‐PTV, mean WB‐PTV D2%, and mean WB‐PTV D98% were 34.9±0.3 Gy,33.2±0.4 Gy, and 26.0±0.4 Gy, respectively. Accordingly, WB‐PTV received the prescription dose of 30 Gy and mean V30 was 90.5%±0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4±0.3 Gy,11.2±0.3 Gy, and 15.6±0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23×0.02 and 0.96×0.02, respectively. The maximum point dose to WB‐PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC‐WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC‐WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719×44 and 2.34×0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1±0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per ...

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Prophylactic Cranial Irradiation for Patients with Small-Cell Lung Cancer in Complete Remission

Abstract: Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission.

Cited by 1,559 publications

References 29 publications

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

Potential for reduced radiation‐induced toxicity using intensity‐modulated arc therapy for whole‐brain radiotherapy with hippocampal sparing

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