- Email: [email protected]
122 Small cell lung carcinoma: experience in patients treated with initial chemotherapy or sequential chemotherapy plus radiotherapy 2005–2010
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Posters, 9th Annual BTOG Conference, 2011: Small cell lung cancer
Median age at diagnosis was 67.6 yrs (range 53.2 81.0 years). 12 pts (57%) were male. Following PET scanning, 9 pts (42.3%) were upstaged to ES. There were no difference in age (p = 0.94) or gender distribution (p = 0.63) between LS & ES. Sites of extrathoracic disease were liver (7), bone marrow (2), bones (1), and retroperitoneal lymph nodes (1). The T- and N- staging distribution of the subgroups were tabulated below. Predisposition to ES were not correlated with larger T-size (p = 0.25) or higher N-stage (p = 0.33). For the entire cohort, 7 pts have died, 2/12 (16.7%) and 5/9 (55.6%) of LS & ES, respectively (p = 0.08). Conclusion: Significant number of pts harbour occult extra-thoracic metastases. In our study, T- and N- staging did not correlate to higher rates of extra-thoracic disease. PET scanning may help identify patients with higher rates of occult metastases but it is unclear yet whether this correlates with inferior survival.
Of 343 patients who were seen for an oncology opinion, 323 received chemotherapy (94%). Median age of treated patients was 68.5 years, (range 32 93). Only 24% had limited stage (LS) disease. Of those receiving treatment a prognostic score (Manchester Score Cerny 1987) was available for 79%. The Poor, Intermediate and Good prognostic groups contained 15%, 52% and 33% of patients respectively. For treated patients, median survival from diagnosis for LS-SCLC was 13.6 months and for extensive stage 6.5 months. Survival at 1-year was 59% and 18% respectively. At 18 months OS was 42% and 4% and at 5 years 14.6 and 0% respectively. OS from diagnosis for patients in the Good, Intermediate and Poor prognostic groups was 11.0, 7.2 and 4.1 months respectively. Conclusion: prognosis for patients unsuitable for concurrent chemoradiation remains poor and little changed over the last 20 years.
121 STOMP: Small cell lung cancer trial of olaparib (AZD2281) as maintenance programme a randomised, double blind, multicentre NCRN phase II trial
Reference(s) Pretreatment prognostic factors and scoring system in 407 small-cell lung cancer patients. Cerny, T et al. Int J. Cancer: 39, 146 149 (1987).
P.J. Woll1 , H. Jarrett2 , L. Billingham2 . 1 Weston Park Hospital, University of Sheffield, United Kingdom, 2 CRUK Clinical Trials Unit, University of Birmingham, United Kingdom Background: PARP inhibitors have activity in patients with BRCA mutations because they are rendered unable to repair DNA damage in tumours. However, there is accumulating evidence that other (more common) tumours have ‘BRCA-ness’ through accumulation of alternative mutations in DNA repair pathways. Chemoresistant SCLC commonly have multiple abnormalities in oncogenic and tumour suppressor pathways, including p53 (80%), Rb (>90%), FHIT (80%) and RASSF1 (90%). These result in increased cell proliferation and DNA damage requiring repair. Recent data have shown that the association of these with defects in DNA repair pathways, including NBS1, ATM, RAD51, Chk1/2 and PTEN may make SCLC cells susceptible to DNA damage. There is also limited in vitro data for single agent activity of olaparib (a potent PARP inhibitor) in SCLC. SCLC has a high response rate to first line chemo/radiotherapy, but chemoresistant relapse is common and fatal. We will therefore test olaparib as a maintenance treatment in patients who have achieved a response to first line therapy. Study population: Patients with SCLC and PR or CR after first line therapy, comprising at least 3 cycles of chemotherapy with platinum + etoposide +/ radiotherapy. Study treatment must start within 21 days of the last RT fraction or 42 days of the start of the last chemo cycle. Trial design: Randomised, double blind, multicentre, phase II trial. Patients will be randomised to olaparib or placebo. Treatment is given by mouth for 2 years or until PD. The primary endpoint is PFS at 4 months. 128 patients are required. Relevant translational studies are planned. Timelines: The trial has been developed under the AstraZeneca/NCRN collaboration. It has CTAAC approval and has been submitted for ethics and regulatory approvals. Expressions of interest should be via [email protected]. The trial will open in Q1 2011. 122 Small cell lung carcinoma: experience in patients treated with initial chemotherapy or sequential chemotherapy plus radiotherapy 2005 2010 P. Taylor, Z. Akram, C. Out, Y. Summers, N. Thatcher. Pulmonary Oncology Unit, Wythenshawe Hospital, Manchester, United Kingdom The experience of SCLC patients treated at Wythenshawe Hospital over a 6-year period was reviewed. Patients suitable for concurrent chemoradiation are treated at another institution (Christie Hospital) so a higher proportion of patients had extensive stage disease and poorer prognostic factors than would otherwise be expected.
123 Small cell lung cancer overall survival, incidence of brain metastases and use of prophylactic cranial irradiation for patients treated in Cambridge during 2005 2009 S.V. Harden1 , D. Saunders2 , L. Magee3 , N. Ainsworth1 . 1 Department of Oncology, Addenbrookes Hospital, Cambridge, United Kingdom, 2 Clinical School, Addenbrookes Hospital, Cambridge, United Kingdom, 3 Papworth Hospital, Cambridgeshire, United Kingdom Introduction: Small cell lung cancer (SCLC) has a poor prognosis and commonly metastasises to the brain. Recently prophylactic cranial irradiation (PCI) after chemotherapy has been shown to improve overall survival in extensive as well as limited stage SCLC. This led to a local change in practice in June 2007 to offer PCI to both extensive and limited stage SCLC patients who responded to chemotherapy. Local survival data and the effect of PCI on clinical outcomes was assessed. Methods: Three hospital databases were retrospectively searched for Cambridgeshire patients with a histological diagnosis of SCLC made between 2005 and 2009. Clinical information on staging, treatment, incidence of brain metastases and date of death was gathered. Data was analysed using GraphPad Prism 4.0 and Instat 3.0 (www.graphpad.com). Results: 176 patients were treated for SCLC. 106 (60%) had extensive stage and 70 (40%) limited stage disease. Chemotherapy was given to 61/70 (87%) limited stage patients and 66/106 (62%) extensive stage patients. Overall 72% (127/176) patients received chemotherapy. PCI post-chemotherapy was given to 39/61(64%) limited and 18/66 (27%) extensive stage patients (15/18 since June 2007). For limited stage patients median survival with PCI was 19.1 months and 14.2 months without PCI (p = 0.259). For extensive stage patients median survival with PCI was 10.8 months, and 6.0 months without PCI (p = 0.031). Brain metastases developed after chemotherapy in 30% patients who did not receive PCI compared to 12% patients receiving PCI (p = 0.026). Conclusion: Our local outcome data compares well with published data on survival for SCLC and supports the use of PCI in extensive as well as limited stage patients. We are now investigating whether a subgroup of SCLC patients most at risk for developing brain metastases can be identified in advance, using novel magnetic resonance imaging techniques within the NCRI Lung Cancer CSG approved CLUB-01 study.
Posters, 9th Annual BTOG Conference, 2011: Small cell lung cancer
Median age at diagnosis was 67.6 yrs (range 53.2 81.0 years). 12 pts (57%) were male. Following PET scanning, 9 pts (42.3%) were upstaged to ES. There were no difference in age (p = 0.94) or gender distribution (p = 0.63) between LS & ES. Sites of extrathoracic disease were liver (7), bone marrow (2), bones (1), and retroperitoneal lymph nodes (1). The T- and N- staging distribution of the subgroups were tabulated below. Predisposition to ES were not correlated with larger T-size (p = 0.25) or higher N-stage (p = 0.33). For the entire cohort, 7 pts have died, 2/12 (16.7%) and 5/9 (55.6%) of LS & ES, respectively (p = 0.08). Conclusion: Significant number of pts harbour occult extra-thoracic metastases. In our study, T- and N- staging did not correlate to higher rates of extra-thoracic disease. PET scanning may help identify patients with higher rates of occult metastases but it is unclear yet whether this correlates with inferior survival.
Of 343 patients who were seen for an oncology opinion, 323 received chemotherapy (94%). Median age of treated patients was 68.5 years, (range 32 93). Only 24% had limited stage (LS) disease. Of those receiving treatment a prognostic score (Manchester Score Cerny 1987) was available for 79%. The Poor, Intermediate and Good prognostic groups contained 15%, 52% and 33% of patients respectively. For treated patients, median survival from diagnosis for LS-SCLC was 13.6 months and for extensive stage 6.5 months. Survival at 1-year was 59% and 18% respectively. At 18 months OS was 42% and 4% and at 5 years 14.6 and 0% respectively. OS from diagnosis for patients in the Good, Intermediate and Poor prognostic groups was 11.0, 7.2 and 4.1 months respectively. Conclusion: prognosis for patients unsuitable for concurrent chemoradiation remains poor and little changed over the last 20 years.
121 STOMP: Small cell lung cancer trial of olaparib (AZD2281) as maintenance programme a randomised, double blind, multicentre NCRN phase II trial
Reference(s) Pretreatment prognostic factors and scoring system in 407 small-cell lung cancer patients. Cerny, T et al. Int J. Cancer: 39, 146 149 (1987).
P.J. Woll1 , H. Jarrett2 , L. Billingham2 . 1 Weston Park Hospital, University of Sheffield, United Kingdom, 2 CRUK Clinical Trials Unit, University of Birmingham, United Kingdom Background: PARP inhibitors have activity in patients with BRCA mutations because they are rendered unable to repair DNA damage in tumours. However, there is accumulating evidence that other (more common) tumours have ‘BRCA-ness’ through accumulation of alternative mutations in DNA repair pathways. Chemoresistant SCLC commonly have multiple abnormalities in oncogenic and tumour suppressor pathways, including p53 (80%), Rb (>90%), FHIT (80%) and RASSF1 (90%). These result in increased cell proliferation and DNA damage requiring repair. Recent data have shown that the association of these with defects in DNA repair pathways, including NBS1, ATM, RAD51, Chk1/2 and PTEN may make SCLC cells susceptible to DNA damage. There is also limited in vitro data for single agent activity of olaparib (a potent PARP inhibitor) in SCLC. SCLC has a high response rate to first line chemo/radiotherapy, but chemoresistant relapse is common and fatal. We will therefore test olaparib as a maintenance treatment in patients who have achieved a response to first line therapy. Study population: Patients with SCLC and PR or CR after first line therapy, comprising at least 3 cycles of chemotherapy with platinum + etoposide +/ radiotherapy. Study treatment must start within 21 days of the last RT fraction or 42 days of the start of the last chemo cycle. Trial design: Randomised, double blind, multicentre, phase II trial. Patients will be randomised to olaparib or placebo. Treatment is given by mouth for 2 years or until PD. The primary endpoint is PFS at 4 months. 128 patients are required. Relevant translational studies are planned. Timelines: The trial has been developed under the AstraZeneca/NCRN collaboration. It has CTAAC approval and has been submitted for ethics and regulatory approvals. Expressions of interest should be via [email protected]. The trial will open in Q1 2011. 122 Small cell lung carcinoma: experience in patients treated with initial chemotherapy or sequential chemotherapy plus radiotherapy 2005 2010 P. Taylor, Z. Akram, C. Out, Y. Summers, N. Thatcher. Pulmonary Oncology Unit, Wythenshawe Hospital, Manchester, United Kingdom The experience of SCLC patients treated at Wythenshawe Hospital over a 6-year period was reviewed. Patients suitable for concurrent chemoradiation are treated at another institution (Christie Hospital) so a higher proportion of patients had extensive stage disease and poorer prognostic factors than would otherwise be expected.
123 Small cell lung cancer overall survival, incidence of brain metastases and use of prophylactic cranial irradiation for patients treated in Cambridge during 2005 2009 S.V. Harden1 , D. Saunders2 , L. Magee3 , N. Ainsworth1 . 1 Department of Oncology, Addenbrookes Hospital, Cambridge, United Kingdom, 2 Clinical School, Addenbrookes Hospital, Cambridge, United Kingdom, 3 Papworth Hospital, Cambridgeshire, United Kingdom Introduction: Small cell lung cancer (SCLC) has a poor prognosis and commonly metastasises to the brain. Recently prophylactic cranial irradiation (PCI) after chemotherapy has been shown to improve overall survival in extensive as well as limited stage SCLC. This led to a local change in practice in June 2007 to offer PCI to both extensive and limited stage SCLC patients who responded to chemotherapy. Local survival data and the effect of PCI on clinical outcomes was assessed. Methods: Three hospital databases were retrospectively searched for Cambridgeshire patients with a histological diagnosis of SCLC made between 2005 and 2009. Clinical information on staging, treatment, incidence of brain metastases and date of death was gathered. Data was analysed using GraphPad Prism 4.0 and Instat 3.0 (www.graphpad.com). Results: 176 patients were treated for SCLC. 106 (60%) had extensive stage and 70 (40%) limited stage disease. Chemotherapy was given to 61/70 (87%) limited stage patients and 66/106 (62%) extensive stage patients. Overall 72% (127/176) patients received chemotherapy. PCI post-chemotherapy was given to 39/61(64%) limited and 18/66 (27%) extensive stage patients (15/18 since June 2007). For limited stage patients median survival with PCI was 19.1 months and 14.2 months without PCI (p = 0.259). For extensive stage patients median survival with PCI was 10.8 months, and 6.0 months without PCI (p = 0.031). Brain metastases developed after chemotherapy in 30% patients who did not receive PCI compared to 12% patients receiving PCI (p = 0.026). Conclusion: Our local outcome data compares well with published data on survival for SCLC and supports the use of PCI in extensive as well as limited stage patients. We are now investigating whether a subgroup of SCLC patients most at risk for developing brain metastases can be identified in advance, using novel magnetic resonance imaging techniques within the NCRI Lung Cancer CSG approved CLUB-01 study.