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J. Roth
Moderator of
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HOD1 - Mondays Highlights of the Day - Radiotherapy, Radiology and Surgery (ID 226)
- Event: WCLC 2013
- Type: Highlight of the Day Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 2
- Moderators:J. Roth
- Coordinates: 10/29/2013, 07:00 - 08:00, Bayside Auditorium A, Level 1
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Interventions, Radiology and Surgery (ID 4043)
07:30 - 08:00 | Author(s): M. Tsuboi
- Abstract
- Presentation
Abstract not provided
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HOD1.1 - Radiotherapy (ID 4042)
07:00 - 07:30 | Author(s): M. Werner-Wasik
- Abstract
- Presentation
Abstract not provided
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MO22 - Advanced Disease and Outcomes (ID 103)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Surgery
- Presentations: 12
- Moderators:T. Yano, J. Roth
- Coordinates: 10/30/2013, 10:30 - 12:00, Parkside 110 A+B, Level 1
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MO22.01 - High procedure volume is strongly associated with improved survival after lung cancer surgery (ID 1704)
10:30 - 10:35 | Author(s): M. Luchtenborg, S.P. Riaz, V.H. Coupland, E. Lim, E. Jakobsen, M. Krasnik, R. Page, M. Lind, M.D. Peake, H. Moller
- Abstract
- Presentation
Background
Surgical resection is the first line treatment offered to patients with early stage non-small cell lung cancer (NSCLC) who are considered medically fit. Many studies have shown that patients undergoing surgery for lung cancer benefit from receiving treatment in hospitals where high numbers of lung cancer resections are carried out. This study explores the association between hospital volume and survival among all NSCLC patients diagnosed in England who underwent surgical resection and takes into account the differences in case selection and propensity to resect.Methods
We analysed data on 134,293 patients with NSCLC diagnosed in England between 2004 and 2008 of whom 12,862 (9·6%) underwent surgical resection. Hospital volume was defined according to the number of patients with resected lung cancer in each hospital in each year of diagnosis. Cox proportional hazard regression analyses were used to assess the association between hospital volume and survival among resected patients. We calculated multivariable hazard ratios according to hospital volume, with adjustment for potential confounders (sex, age, socioeconomic deprivation, comorbidity and resection quintile). In addition, to account for the risk of death potentially varying between groups of patients treated within a given hospital, a shared frailty Cox model was used, with hospital as a random effect. The follow-up period was divided into three pre-defined periods: 0-30 days, 31-365 days and >365 days post-surgery.Results
There was increased survival in hospitals performing more than 150 surgical resections compared with those carrying out less than 70 [HR 0·78 (95% CI 0·67-0·90), p~trend~ <0·01]. The association between hospital volume and survival was present in all three periods of follow-up, but the magnitude of the association was greatest in the period 0-30 days (HR for the 150+ hospital volume group compared with less than 70: 0·58, 95% CI 0·38-0·89) and smallest in the period after 365 days (HR 0·84, 95% CI 0·71-0·99).Conclusion
High volume hospitals have higher resection rates, operate on patients who are older, have lower socioeconomic status, more comorbidities and despite that they achieve better survival, most notably in the early post-operative period.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22.02 - Resection rate, as a measure of the effectiveness of surgical treatment of lung cancer (ID 2428)
10:35 - 10:40 | Author(s): T.M. Orlowski, P. Rudzinski
- Abstract
- Presentation
Background
Surgery is the most effective way to treat lung cancer. There are significant differences between countries in the effectiveness of surgical treatment. The resection rate differe from 10 to over 20% in EuropeMethods
The National Registry of lung cancer in Poland comprises over 95% of patients with NSCLC treated with surgery. Resection rate (RR) is monitored for 20 years in Poland. Each year RR is calculated by the following formula: R R = (number of resected patients with NSCLC/ number of new cases) x 100 This ratio is calculated for each and even the smallest administrative area (16 provinces and 380 districts). To achieve such a result- the patient's place of residence is taken into account rather than a place where he had his surgery. This allows to determine how many of the patients in particular area have been diagnosed in certain stage of acceptance (mainly I and II) In year 2012, 3591 patients had surgery in Poland. The incidence of NSCLC this year was 22 348 new cases.Results
The RR in Poland in 2012 was 16.1%. The difference in many provinces ranged from 10.2% - 22%. In few districts the RR was reported from 0% - 46%. 79% of patients were in stage I and II, 11.2% in IIIa, 2.7% in IIIb and and 1.9% in stage IV. Comparing to 2011, resection rate increased by 5%, and within five years - 16.8%. Since 2010 in the areas with the lowest RR a screening program with low-dose computed tomography was implemented. The RR increased from 1,2 to 22% in majority of districts (14/16)Conclusion
1 Implementation of the resection rate allows to monitor the effectiveness of early diagnosis of lung cancer in different areas 2 Monitoring of the resection rate allows to improve the efficiency of diagnosis of lung cancer in areas where detection was low. 3. Regular evaluation of the RR supports the efforts to improve the results of surgical tratment of NSCLCOnly Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22.03 - Postoperative Rehabilitation and Follow-up - a randomized study. (ID 2422)
10:40 - 10:45 | Author(s): E. Jakobsen, O. Dan Joergensen, L. Ladegaard, S. Petersen, P. Mikkelsen, I. Aagaard, P. Licht
- Abstract
- Presentation
Background
The importance of postoperative follow-up and rehabilitation after lung cancer surgery remains a controversial topic. Previous studies have showed that follow-up programs did not influence survival but at that time there was little focus on the effects of rehabilitation. Introduction of new diagnostic procedures, improvements in treatment modalities and increasing awareness on quality of life after treatment has changed guidelines and recommendations for follow-up programs. There is little evidence for these recommendations which prompted us to conduct a randomized study to evaluate the effect of an intense follow-up program on survival and quality of life for patients undergoing surgery for lung cancer (NSCLC).Methods
Between January 2003 and April 2008 a total 197 NSCLC patients were included in the study after undergoing surgical resection (wedge, lobectomy or pneumonectomy) through a posterolateral thoracotomy. Adjuvant chemotherapy was offered to stage Ib - IIIa. Postoperatively patients were randomized to either active rehabilitation and follow-up (POREFU, N=103) or passive follow-up (Standard, N=94). Patients in the POREFU group had intensive follow-up in the form of annual clinical evaluation, chest X-ray, chest CT, bronchoscopy and EBUS (Endobronchial Ultrasound) for 5 years. In the POREFU group patients were also evaluated by a nurse and a physiotherapist after 6 weeks, 6 months and at annual controls. When indicated, interventions were established to correct patient symptoms. Patients in the standard treatment group were offered a chest X-ray one year after surgery and a clinical examination by their family doctors upon request. Quality of life in both groups was assessed after 6 weeks, 6 months, 12 months and 2, 3, 4 and 5 years evaluating EORTC QLQ-C30/LC13. All survivors were followed for 5 years.Results
Figure 1There was no significant difference in survival between the two groups (Kaplan Meier plot). There was a significant difference between the two groups in favour of active follow-up regarding Global health status as well as “Physical”, “Role” and “Emotional” functioning and POREFU patients had significant less pain and fatigue. There was no statistical significant improvement of other symptoms or functional issues.Conclusion
This randomized trial shows that a follow-up program with an additional focus on rehabilitation and intervention towards reported symptoms in patients operated for NSCLC significantly improves quality of life but has no effect on overall survival.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22.04 - Standardising the Management of Patients Following Lung Resection: Does It Improve Outcome? (ID 2114)
10:45 - 10:50 | Author(s): A.J. Sharkey, J. Coad, R. Owen-Smith, A. Cale, M. Chaudhry, S. Griffin, M. Loubani, M. Cowen
- Abstract
- Presentation
Background
There is marked variation in the management of Thoracic surgical patients post-operatively, both between individual surgeons and surgical centres. This lack of standardisation can lead to staff and patient dissatisfaction, and differing outcomes for patients. In 2012 we introduced a more standardised approach to the management of patients undergoing Thoracic surgery under the care of one consultant (Consultant A). This was based on the ‘fast-track’ protocol published in 2001 by Cerfolio et al. We aimed to determine whether this approach to patient management has affected patient outcome.Methods
Data for all patients undergoing lung resection at a single centre from April 2012 to March 2013 were collected. The patients were split into two groups, those under the care of Consultant A (group A), and those under the care of the remaining 4 consultants (group B). Group A were managed according to the new standardised pathway which included; stopping the routine use of suction unless clinically required, chest drain removal with cessation of an air leak and drainage below 400mls in 24 hours, and epidural catheter removal on post-operative day 2. Those in group B were managed according to the instructions of the operating Consultant, or the surgical registrars covering the ward. Pre-operative, operative and post-operative data were collected and analysed. Patients were then propensity matched using operation and age.Results
Two hundred and thirty one patients were identified. Overall mean length of stay for all patients in group A was 5.65 days (SD±4.68), and in group B; 9.97 days (SD±12.06), p<0.001. Of these patients 94 were suitable for propensity matching. There were no significant differences found in the proportion of patients with benign versus malignant pathology, the number with primary lung cancer, or in the stage of the resected primary lung cancer. In-hospital mortality for both groups was one patient (2.13%). There was a lower number of drains inserted peri-operatively in group A patients (p<0.001). Mean time to drain removal (all drains) was 3.42 days (SD±6.35) for group A and 4.24 days (SD±3.08) for group B, p=0.026. Mean length of stay for group A was 6.00 days (SD± 4.86) and for group B 10.33 days (SD±19.29), p=0.042.Conclusion
Standardising care following surgery has been shown to improve patient safety, and both patient and staff satisfaction. We have found that reducing variation, and following a validated management pathway, significantly reduces the time to chest drain removal and in-hospital length of stay for patients undergoing lung resection for any pathology. We are currently analysing the various elements of the pathway to determine which specific factors impact patient outcome. Further work is required to determine the effect these differences have on patient reported outcome measures, including overall satisfaction.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22.05 - Surgery in octogenarians with early stage non-small cell lung cancer: A SEER database analysis (ID 2923)
10:50 - 10:55 | Author(s): A.K. Ganti, V. Shostrom, A. Marr, K.M. Islam, R.P. Lackner, K. Trujillo, A. Kessinger
- Abstract
- Presentation
Background
Surgical resection is the standard of care for patients with early stage non-small cell lung cancer (NSCLC). However outcomes in older patients, especially octogenarians, following resection have not been studied in detail. This analysis was undertaken to evaluate the variations in patterns of care over time and outcomes following resection in octogenarians with early stage NSCLC.Methods
Patients 80 years of age and older diagnosed with clinical stages I and II NSCLC, between 1988 and 2007, were identified from the SEER database. Data abstracted included age at diagnosis, stage, gender, race, histology, year of diagnosis and cause of death. The type of surgical resection was not available for a majority of patients and hence was not considered. Overall survival was estimated as the time from the date of diagnosis to death, or date of last contact (if censored). Factors associated with survival were assessed using regression analysis based on the Cox proportional hazards model. Temporal trends in survival were compared using log-rank test. Lung cancer specific survival (LCSS) was also estimated in these patients and temporal trends were compared using log-rank tests.Results
Six hundred and forty-nine patients ≥80 years of age, who underwent surgical resection for stages I and II NSCLC, were identified. The majority of these patients had stage I disease (n=549), were white (n=586) and had an adenocarcinoma (n=325). Females comprised 50.6% of stage I, but only 37% of stage II patients. Factors associated with worse overall survival on multivariate analysis in this cohort were: increasing age [Hazard ratio (HR) - 1.08; 95% CI - 1.03, 1.12], male gender (HR - 1.33; 95% CI - 1.07, 1.65), stage II (HR - 2.21; 95% CI - 1.71, 2.87) and squamous histology (HR - 1.36; 95% CI - 1.07, 1.74). The percentage of patients undergoing surgery increased over time. Of the patients who underwent surgery 8.6% were diagnosed between 1988-1992, 16% between 1993-1997, 24.2% between 1998-2002 and 51.2% between 2002-2007. Despite this the median survival was not significantly different over these time periods. Median survivals for the four different time periods were as follows: 1988-1992 – 3.9 years; 1993-1997 – 3.2 years; 1998-2002 – 3.8 years; 2002-2007 – 3.3 years (p = 0.09). These are comparable to those reported previously in younger patients (ages 65-75 years) (5.92 years - stage I, 2.6 years - stage II). Similarly lung cancer specific survival was not significantly different between the different time points. Median LCSS for the four time periods were 9.2 years, 6.8 years, 7.9 years, and not reached, respectively (p = 0.51).Conclusion
Among octogenarians who had surgical resection for lung cancer, increasing age, male gender, higher stage and squamous histology were associated with worse survival. Despite an increased incidence of surgical resection for octogenarians, outcomes remained unchanged between 1988 and 2007. Octogenarians, when carefully selected, are capable of experiencing a similar advantage provided by surgical resection of early stage non small cell lung cancer as younger patients.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22.06 - DISCUSSANT (ID 3927)
10:55 - 11:10 | Author(s): S. Knight
- Abstract
- Presentation
Abstract not provided
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MO22.07 - Local treatment of oligometastatic recurrence after surgery for non-small cell lung cancer. (ID 932)
11:10 - 11:15 | Author(s): T. Yano, T. Okamoto, A. Haro, S. Fukuyama, D. Kawano, Y. Morodomi, T. Yoshida, M. Kohno, Y. Maehara
- Abstract
- Presentation
Background
We previously reported a retrospective study indicating the prognostic impact of local treatment of postoperative oligometastases in patients with non-small cell lung cancer (NSCLC) (Yano T et al. J Surg Oncol 2010;102:852-855). However, previous studies have not been sufficient to determine the therapeutic significance of local treatment for postoperative oligometastases since the conclusions were based on retrospectively collected data and the assessment of overall survival. In the present study, we prospectively observed postoperative oligometastatic patients and investigated the effects of local treatment on progression-free survival (PFS).Methods
Using a prospectively maintained database of patients with completely resected NSCLC treated between October 2007 and December 2011, we identified 52 consecutive patients with postoperative recurrence. Of these patients, 31 suffering from distant metastases alone without primary site recurrence were included in this study. In order to exclude cases of second primary carcinoma of the lungs, the criteria of Martini and Melamed, modified by Antakli et al., were used to differentiate between second primary lung cancer and pulmonary metastasis. According to the definition of ‘oligometastases’ as limited recurrence potentially controlled with local treatment, 17 patients had oligometastatic disease. The number of metastases was less than four.Results
The oligometastatic sites included the lungs in five patients, the brain in four patients, bone in four patients, the lungs and brain in two patients, the adrenal glands in one patient and soft tissue in one patient. Fifteen of the 17 patients first received local treatment. Three patients (lung, adrenal gland, soft tissue) underwent surgical resection, and the remaining 12 patients received radiotherapy. The median PFS was 33 months in the oligometastatic patients who received local treatment. There were seven patients with a PFS of longer than two years. The metastatic sites in these patients varied, and the number of lesions in three patients was two or three. On the other hand, the two remaining patients first received a systemic chemotherapy of their own selection. The PFS of these two patients was five and 15 months, respectively.Conclusion
Both our previous retrospective study and the present study favor a choice of local treatment in patients with postoperative oligometastatic NSCLC.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22.08 - Surgical Resection of Stage IIIA-N2 non-small cell lung cancer: Should we still talk about the futile thoracotomy? (ID 825)
11:15 - 11:20 | Author(s): O. Mercier, E. Fadel, M. De Perrot, T. Pierard, S. Mussot, D. Fabre, F. Leroy Ladurie, B. Besse, C. Le Pechoux, T. Le Chevalier, P. Dartevelle
- Abstract
- Presentation
Background
Stage IIIA-N2 non-small cell lung cancer (NSCLC) is currently mainly managed with chemotherapy and radiation therapy with limited outcome. Whether surgical resection should be offered to patients with resectable IIIA-N2 NSCLC as part of a multi-modality approach with adjuvant or neoadjuvant treatment remains unclear. We sought to determine the long-term result of resected IIIA-N2 NSCLC in a single institution.Methods
We reviewed the charts from a consecutive series of 263 patients with a mean age of 62 years (range, 37-68) undergoing lung resection and complete en bloc lymph node dissection for IIIA-N2 NSCLC from 01/2000 to 12/2011. Clinical N2 (cN2) patients were diagnosed preoperatively on chest CT scan and/or PET scan and were histologically proven by mediastinoscopy or EBUS. Patients with cN2 with a single site of mediastinal disease were occasionally treated with surgery upfront followed by adjuvant chemotherapy with or without radiation (cN2 adj, n=70). The remaining patients with cN2 disease were treated with neoadjuvant therapy followed by surgery (cN2 neoadj, n=55). Minimal N2 patients were diagnosed postoperatively on final pathology report and received adjuvant therapy (mN2, n=138).Results
Lung resection was a pneumonectomy in 75 patients and a lobectomy in 188 patients with a post-operative mortality of 1.3% and 3.1%, respectively. Adjuvant chemo- or chemoradiation therapy was administered in 181 patients. The overall 5-year survival was 43.6%, with no significant difference between the type of lung resection (pneumonectomy: 38.9% vs. lobectomy: 45.5%, p=0.18) or the number of mediastinal lymph node site involvement (1 site 44.8% vs. 37,7% for multiple sites, p=0.9). Long-term survival tended to be better for mN2 compared to cN2 (5-year survival of 50.4% vs. 35.9%, respectively; p=0.08). However, survival for cN2 was similar between neoadjuvant and adjuvant therapy (5-year survival of 30.3% vs. 40.2%, respectively; p=0.53). The number of mediastinal lymph node site involvement did not impact survival in patients with cN2 disease (1 site 37.6% vs 27.6% for multiple sites, p=0.59).Conclusion
Surgery for Stage IIIA-N2 NSCLC achieved good long-term survival when combined with chemotherapy or chemo-radiation therapy in well selected patients. Long-term survival was similar in patients with clinical N2 disease whether they received adjuvant or neoadjuvant therapy. Surgery should be considered as part of a multimodality treatment for patients with stage III-N2 NSCLC.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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- Abstract
- Presentation
Background
The objectives of this study were to report the surgical techniques and clinical outcome of thoracoscopic half carina resection and thoracoscopic bronchial sleeve resection for central lung cancer.Methods
Between January 2011 and November 2012, 675 patients with lung cancer underwent radical surgery by thoracoscopy, 49 (7.3%) underwent bronchial sleeve resection. Among 49 patients, 20 (41%) received thoracoscopic bronchial sleeve lobectomy. Perioperative variables and postoperative outcomes of these cases were analyzed to evaluate the technical feasibility and safety of this operation.Results
In one patient, right upper lung sleeve resection was combined with half-carinal resection and reconstruction. In another, right medial lung sleeve resection was combined with lower right dorsal segment resection. The average time of surgery was 239 min (range, 142-330 min, 239±51 min), and the average time of airway reconstruction was 44 min (range, 22-75 min, 44±17 min). The intraoperative blood loss averaged 207 ml (range, 80-550 ml, 207±96 min). The median postoperative hospital stay was 10 days (interquartile range, 8-12 days). Postoperatively, extubation was achieved in the recovery room without further need for mechanical ventilation. None of the patients developed anastomotic leak. Perioperative mortality was not observed.Conclusion
Thoracoscopic bronchial sleeve resection can be considered a feasible and safe operation for selected patients with central lung cancer. The complicated anastomosis technique of half carina resection was feasible.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22.10 - Surgery after Concurrent Chemo-Radiation with 55 Gy in 20 Fractions over four weeks with full dose Platinum and Vinorelbine (ID 3447)
11:25 - 11:30 | Author(s): J. Maguire, J. Littler, V. Kelly
- Abstract
- Presentation
Background
Concurrent chemo-radiation is the standard of care for patients with inoperable stage III NSCLC and good performance status. Following concurrent chemo-radiation some patients may have operable disease, and surgery may be considered to improve the prospects of cure for patients with negative mediastinal nodes and evidence of residual activity in the primary tumour. Surgery is usually not considered for patients who have received radiation doses higher than 45 Gy in 2 Gy daily fractions because of the perceived risk of post operative complications.Methods
Our standard concurrent chemo-radiotherapy regimen comprises 55 Gy in 20 fractions of 2.75 Gy per day, given over four weeks with cisplatinum 20 mg/m[2] given with radiotherapy fractions 1-4 and 16-19, and vinorelbine 15 mg/m[2 ]IV (40 mg/m[2] orally for patients without dysphagia) with fractions 1, 6, 15 and 20. Twenty-two patients at the Liverpool Heart and Chest Hospital have undergone thoracotomy with a view to resection of residual tumour after completion of this concurrent chemo-radiotherapy schedule.Results
Resection of residual disease was achieved in 21 out of 22 cases. In one patient, resection was not possible due to dense fibrosis and adhesions at the tumour site. Five patients underwent pneumonectomy, 15 lobectomy and one underwent wedge resection. There was one death in the 30 days following surgery and one patient developed a fistula at 4 months. Histological examination of resection specimens confirmed complete histological response in 14 out of 21 cases (66%). Median survival for was 93.8 months, with 5 year survival of 58.8% and 27.6% of patients surviving 10 years from start of treatment.Conclusion
Surgical resection is feasible after concurrent chemo-radiation to a dose of 55 Gy in 20 fractions over 4 weeks. The remarkably high complete histological response rate in this series confirms the effectiveness of a strategy to minimise accelerated repopulation by using hypofractionated radiotherapy with cisplatinum and vinorelbine over four weeks.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22.11 - Prospective Study of Surgery with Curative Intent and Intraoperative Photodynamic Therapy to Achieve Long-term Pleural Control and Improve Overall Survival for Patients with Non-small Cell Lung Cancer with Pleural Dissemination (ID 3141)
11:30 - 11:35 | Author(s): C.B. Simone, K.M. McKay, M.J. Culligan, D. Sterman, E. Alley, T.M. Busch, E. Glatstein, S.M. Hahn, K.A. Cengel, J. Friedberg
- Abstract
- Presentation
Background
Non-small cell lung cancer (NSCLC) with pleural spread carries a dismal prognosis of 6-9 months median survival. Standard treatment is palliative chemotherapy. Surgery typically has no role, with studies showing no overall survival (OS) benefit and high rates of local recurrence of up to 90% due to microscopic residual disease following resection. This study investigated the use of surgery with the intent of achieving a gross total resection and intraoperative photodynamic therapy (PDT) to target microscopic residual disease for patients with NSCLC with pleural metastasis to improve local control and OS.Methods
All patients with NSCLC with pleural metastasis treated with definitive surgery and PDT (porfimer sodium, 24hr drug-light interval, 630nm, 30-60J/cm[2]) from 1997-2012 on either of two IRB-approved prospective clinical trials were assessed. Progression-free survival (PFS) and OS were defined as the time from surgery to recurrence and death, respectively, or to last contact. Pleural control was defined as absence of ipsilateral pleural disease after surgery, whereas locoregional control was defined as absence of lung parenchymal or intrathoracic nodal disease.Results
34 consecutive patients were assessed, all with ECOG performance status 0-1. The cohort was 50% male, predominantly Caucasian (85%), and a median of 55yrs at the time of surgery (range, 35-73yrs). Most had adenocarcinoma (79%), clinical N2 nodal metastasis (64%), and received neoadjuvant chemotherapy (94%) and/or radiotherapy (12%). Over half (56%) underwent pneumonectomy, whereas 38% received a lesser anatomic resection. Two patients were found intraoperatively to have unresectable disease due to pericardial effusion (n=1) or trans-diaphragmatic extension (n=1). Pathologic staging was pT4N0 (24%) or pT4N2 (76%). Four patients (3/19 pneumonectomy, 1/13 lung-sparing) suffered peri-operative mortality (day 11-98), with one death attributable to PDT (ARDS, day 11). Following surgery/PDT, 59% of patients received mediastinal radiotherapy (median 50.4Gy/1.8Gy) and 50% received chemotherapy. Pleural recurrence rates and OS were similar for patients undergoing pneumonectomy or other procedures (p>0.05 for both). Cohort median OS was 21.4 months (0.4-161.1 months), and survival rates were 59% at 1yr and 41% at 2yrs. Median overall PFS was 7.5 months, with numerous patients achieving durable disease-free intervals (mean PFS 18.4 months). Median pleural PFS was 13.6 months, with pleural recurrences occurring in only 32%. Overall, 79% experienced recurrence or unresectable disease progression, and distant failure was most commonly observed (53%).Conclusion
This study demonstrates that surgery and intraoperative PDT can achieve durable local control and prolonged survival for NSCLC patients with pleural dissemination. Compared with current standard treatment, which offers a median survival of 6-9 months from pleural metastasis diagnosis, our cohort lived a median of 24.7 months from pleural diagnosis and 21.4 months from surgery/PDT. This study also demonstrates that surgery/PDT can be performed with acceptable morbidity. Distant recurrence was the most common failure, indicating need for improved adjuvant systemic therapy. These results are sufficiently encouraging to warrant further study and suggest that stage IVA NSCLC patients with pleural dissemination, good performance statuses, disease limited to one hemithorax, and of the mind to be aggressive about their disease could be considered for this investigational treatment approach.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO22.12 - DISCUSSANT (ID 3928)
11:35 - 11:50 | Author(s): B.E. Louie
- Abstract
- Presentation
Abstract not provided
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Author of
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MO17 - Radiotherapy I: Stereotactic Ablative Body Radiotherapy (ID 106)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:M. Zwitter, S.K. Vinod
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside 204 A+B, Level 2
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MO17.11 - Stereotactic ablative radiotherapy (SABR) for centrally located early-stage or isolated parenchymal recurrences of non-small cell lung cancer (NSCLC): How to fly in a "no fly zone" (ID 1961)
17:15 - 17:20 | Author(s): J. Roth
- Abstract
- Presentation
Background
SABR has become a standard treatment option for medically inoperable, peripherally located early-stage NSCLC. However, using SABR for centrally located lesions remains challenging because of the potential for severe side effects. Here we sought to validate our previous experience with SABR (50 Gy in 4 fractions) for central lesions, including the dose-volume constraints, and explore a new regimen of 70 Gy in 10 fractions for cases in which dose-volume constraints cannot be met with the previous regimen.Methods
We used 4D-based, volumetric image-guided SABR to treat 101 patients with biopsy-proven and PET/CT-staged centrally located (within 2 cm of bronchial tree, trachea, major vessels, esophagus, heart, pericardium, brachial plexus or vertebral body) T1-2N0M0 tumors (n=82) or isolated lung-parenchyma recurrent lesions (n=19). The treatment period spanned February 2005 through May 2011; follow-up visits (every 3 months for 2 years and every 6 months for the next 3 years) included chest CT or PET/CT. Endpoints were toxicity (CTCAE v3.0), survival, local control, regional control, and distant metastasis.Results
At a median follow-up time of 30.3 months for all patients (40.5 months for those alive), median overall survival time was 56.5 months and 5-year overall survival rate was 49.0%. Three-year actuarial local, regional, and distant control rates were 96.5%, 87.2% and 77.3%. The most common toxicities were chest-wall pain (18% grade 1 and 13% grade 2) and radiation pneumonitis (10.9% grade 2 and 1.9% grade 3). No patient experienced grade 4 toxicity and one patient with tumor invading bronchial tree who received 70 Gy in 10 fractions died from hemoptysis 13 months after SABR. The distance between tumor and chest was associated with chest wall pain (≤1 cm 45% vs >1 cm 17%, p=0.002). Univariate and multivariate analyses showed that for the 82 patients receiving 50 Gy in 4 fractions, mean total lung dose (MLD) >5 Gy or ipsilateral lung V~20~ (iV~20~) >16% were independent predictors of radiation pneumonitis; 3 of 9 patients in that group with D~max~ to brachial plexus >35 Gy experienced brachial neuropathy versus none of the 73 patients with brachial D~max~ ≤ 35 Gy (p=0.001).Conclusion
SABR for centrally located lesions produces clinical outcomes similar to those for peripheral lesions when normal tissue constraints are respected. For 50 Gy in 4 fractions, we recommend MLD ≤5 Gy, lung iV~20~ ≤16%; bronchial tree D~max~ ≤ 38 Gy, V~35~ ≤1 cm[3]; major vessel D~max~≤ 56 Gy, V~40~≤1 cm[3]; esophageal D~max~ ≤35 Gy, V~30~≤1 cm[3 ]; brachial plexus D~max~ ≤35 Gy, V~30~≤0.2 cm[3] and spinal cord D~max~ <25 Gy. Giving 70 Gy in 10 fractions is another option for challenging cases but can produce severe toxicity if significant amounts of critical structures are exposed to ≥70 Gy. Proper selection of cases (based on tumor location and normal tissue constraints) and SABR regimens and volumetric image-guided delivery are all crucial to avoid overdosing critical structures. Typically, a minimum 5-10 mm distance between critical structures and gross tumor is required to meet dose-volume constraints.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.05 - Poster Session 1 - Preclinical Models of Therapeutics/Imaging (ID 156)
- Event: WCLC 2013
- Type: Poster Session
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.05-003 - The PDGFR/Src signaling pathway-targeted therapy with novel TUSC2-nanoparticles and tyrosine kinase inhibitors for human lung cancer (ID 1194)
09:30 - 09:30 | Author(s): J. Roth
- Abstract
Background
The PDGFR is among the significantly mutated pathways and the PDGFR and downstream Src family protein kinases are often aberrantly activated and play important roles in mediating oncogenic signaling and modulating sensitivity to the molecularly-targeted therapy in lung cancer. We have previously shown that the novel tumor suppressor TUSC2 (FUS1) functions as a key mediator in the apoptosis signaling pathway and down-regulates activities of multiple oncogenic protein kinases such as EGFR, PDGFR, Src, and c-Abl in lung cancer cells. A systemic treatment with FUS1-DOTAP:Cholesterol nanoparticles demonstrated a potent antitumor efficacy in preclinical lung cancer animal models and showed promising clinical benefits in advanced lung cancer patients.Methods
In this study, we evaluated a rationalized therapeutic strategy using a combined systemic treatment with the multifunctional FUS1-nanoparticles and the PDGFR kinase inhibitor imatinib (gleevec) or the Src inhibitor Dasatinib or KX2-391 to simultaneously target the dysregulated PDGFR-Src-PI3K-Akt signaling pathways and suppress tumor cell growth by facilitating apoptosis in human lung cancer cells in vitro and in vivo.Results
We have compared the effectiveness of the orally-available Src inhibitor dasatinib (a ATP competitive inhibitor) or KX2-391 (a novel non-competitive inhibitor that interrupts binding of the Src kinase to its substrates) as an single agent or in combination with FUS1-nanopaticles for potentiating their anticancer efficacy in NSCL and SCLC cells. We found that the dasatinib treatment alone showed a moderate level of tumor cell growth arrest and cell viability reduction but a low degree of apoptosis induction in selected NSCLC cells and exhibited a very low degree of tumor cell killing in SCLC cells. In comparison, the KX2 demonstrated a 10-100 fold higher tumor cell killing and apoptosis induction than Dasatinib in more than 20 NSCLC and SCLC cells tested. The ectopic expression by FUS1- nanoparticle-mediated gene transfer in these lung cancer cells markedly enhanced the dasatinib- or KX2-mediated tumor cell killing. The combination treatment with FUS1-nanoparticles and Src inhibitors dramatically reduced their IC50s in NSCLC cells and suppressed NSCLC cells growth through a mechanism of action by a significant induction of apoptosis and the down-regulation of activated EGFR, PI3K, Akt, and Src kinases. Furthermore, the ectopic expression of wt-FUS1 in the PDGFRß-expressing SCLC H128, N417. and NSCLC H358 cell lines inactivated PDGFR oncogenic signaling, as evidenced by a significant reduction in levels of phospho-PDGFRß and downstream phospho-PI3-K and phospho-AKT protein expression, relative to untransfected or lacZ-transfected controls. A combined treatment with FUS1-nanoparticles and the PTK inhibitor imatinib synergistically inhibited growth and induced apoptosis in SCLC and NSCLC cell lines and in preclinical mouse models with N417 SCLC orthotopic lung tumor xenografts.Conclusion
Our findings suggest that a combination of the pro-apoptotic FUS1-nanoparticle with novel PDGFR or Src inhibitors targeting the PDGFR-Src-PI3K-Akt signaling pathway that is significantly mutated and predominantly activated in lung cancer cells could sensitize their response to PDGFR and Src inhibitors by more efficiently inhibiting tumor cell proliferation and survival, facilitating apoptosis, and overcoming drug resistance. (This abstract is supported by NIH/NCI Grants SPORE P50CA70907 and RO1CA116322).
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P1.07 - Poster Session 1 - Surgery (ID 184)
- Event: WCLC 2013
- Type: Poster Session
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.07-010 - Preoperative Flourodeoxyglucose-Positron Emission Tomography Scan with Positive N1 Disease Does Not Predict Worse Survival in Pathologic Stage II Patients (ID 1070)
09:30 - 09:30 | Author(s): J. Roth
- Abstract
Background
The rate of fluorodeoxyglucose uptake measured as standardized uptake value (SUV) on positron emission tomography (PET) of the primary tumor has been correlated with tumor aggressiveness and poor survival in patients with lung cancer. A retrospective review of patients with lung cancer who were treated with surgical resection at MD Anderson Cancer Center (MDACC) was performed to determine if the pre-operative SUV uptake of N1 disease has any prognostic significance in patients with pathologic stage II lung cancer.Methods
We reviewed all patients who underwent surgical resection for lung cancer at MDACC from 1998 to 2011. We evaluated non-small cell lung cancer patients who had at least a lobectomy at MDACC as first mode of surgical therapy who had pathologic stage T1-2 and N1 disease and pre-operative PET-CT scan. We determined the clinicopathologic characteristics of patients who had PET-positive N1 disease and compared them to patients who had PET-negative N1 disease. We also performed Kaplan Meier analysis to determine the survival between the two groups.Results
Among patients who underwent surgical resection for lung cancer at MDACC during this time period, 120 patients met the inclusion criteria for the study. There were 100 stage IIA or T1aN1, T1bN1 or T2aN1 and 20 stage IIB or T2bN1 patients in the study. There were 62 patients (50% of the patients) who had a primary tumor in the periphery of the lung and 58 patients (50% of the patients) who had a primary tumor in the central portion of the lung. Within this group of 120 patients, only 29 patients (24% of the patients) had PET-positive N1 disease. Only 16 out of 58 patients (28%) in the central group and only 13 out of 62 patients (21%) in the peripheral group had PET-positive N1 disease. There was no clinical or pathological difference between the patients who had PET-positive N1 disease and PET-negative N1 disease. The average maxSUV of the primary tumor was 13 ± 10.7 and average maxSUV of the PET-positive N1 disease was 6.3 ± 4.1. Kaplan Meier analysis showed that there was no significant difference in survival between the patients who had PET-positive N1 disease and PET-negative N1 disease.Conclusion
Among patients with pathologic stage II non-small cell lung cancer, preoperative PET scan was very poor at predicting positive pathologic N1 disease. Since it is difficult to predict pN1 disease, operative patients with clinical stage I non-small cell lung cancer should have surgical resection oppose to ablative therapy. Moreover, SUV uptake of N1 disease in patients with pathologic stage II lung cancer did not predict worse survival in pathologic stage II patients. Thus, patients with cN1 disease should undergo surgical resection after appropriate mediastinal staging.
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P3.08 - Poster Session 3 - Radiotherapy (ID 199)
- Event: WCLC 2013
- Type: Poster Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.08-011 - Stereotactic Ablative Radiotherapy: A Potentially Curable Approach to Multiple Primary Lung Cancer (ID 1454)
09:30 - 09:30 | Author(s): J. Roth
- Abstract
Background
Lung parenchymal recurrent or multiple lobe cancer is typically considered to have metastatic disease and treated with palliative approach such as chemotherapy. However, some of these patients may have multiple primary lung cancer (MPLC) that could be potential curable. Surgical resection has been the standard treatment for early-stage multiple primary lung cancer (MPLC). However, a significant proportion of patients with MPLC cannot undergo surgery. We explored here the role of stereotactic ablative radiotherapy (SABR) for patients with MPLC.Methods
We reviewed MPLC cases treated with SABR (50 Gy in 4 fractions) for the second tumor. Four-dimensional CT–based planning/volumetric image-guided treatment was used for all patients. Patients underwent chest CT scanning every 3 months for 2 years after the SABR and then every 6 months for another 3 years. PET scans were recommended at 3–12 months after SABR. Toxic effects were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Effects version 4.Results
For the 101 patients treated with SABR, at a median follow-up interval of 36 months and median overall survival of 46 months, 2-year and 4-year in-field local control rates were 97.4% and 95.7%. 2- and 4-year rates of overall survival (OS) were 73.2% and 47.5% and progression-free survival (PFS) were 67.0% and 58.0%. Patients with metachronous tumors had higher OS and PFS than did patients with synchronous tumors (2-year OS 80.6% metachronous vs. 61.5% synchronous; 4-year OS 52.7% vs. 39.7%; p=0.047; 2-year PFS 84.7% vs. 49.4%; 4-year PFS 75.6% vs. 30.4%; p=0.0001). For patients whose tumors were both of the same histology (meaning that the second lesion could have been a satellite, a metastasis, or a recurrent lesion), the 2-year and 4-year OS rates were 76.4% and 51.2%, which were no different from the OS rates for patients with tumors of different pathology (2-year OS: 66.7% and 4-year OS: 40.5%; p=0.406). The 2- and 4-year OS of patients in whom both tumors were classified as stage I were 76.1% and 55.2%, which was better than the OS rates for the patients whose index tumors were of higher stage (2-year OS 66.7%, 4-year OS 26.6%; p=0.049). For patients whose index tumor was treated with surgery or SABR, the incidence of grade ≥3 radiation pneumonitis was 3% (2/71), but this increased to 17% (5/30) for patients whose index tumor was treated with conventional radiotherapy. Other grade ≥3 toxicities included grade 3 chest wall pain (3/101, 3%) and grade 3 skin toxicity (1/101, 1%).Conclusion
1. SABR achieves an excellent long-term tumor control and promising PFS and OS in early-stage MPLC. 2. Toxicity could happen but within the scope of SABR in stage I disease. 3. Caution should be taken integrating SABR with prior conventional radiotherapy for stage II/III disease. SABR could be an effective alternative to surgery for curative treatment of early-stage MPLC tumors.
