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S. Senan
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MINI 18 - Radiation Topics in Localized NSCLC (ID 139)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 2
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MINI18.03 - Immune Activation in Early Stage Non-Small Cell Lung Cancer (NSCLC) following Stereotactic Ablative Radiotherapy (SABR) and Surgery (ID 2123)
16:55 - 17:00 | Author(s): S. Senan
- Abstract
- Presentation
Background:
An anatomical surgical resection is considered to be the standard of care in fit patients, but non-randomized comparative effectives studies suggest that survival outcomes may be similar following SABR. An antitumor immune microenvironment was found to be a prognostic factor in surgically resected early stage NSCLC. SABR has been reported to activate the immunesystem in malignant diseases via a number of mechanisms. We investigated the impact of both surgery and SABR in early stage NSCLC on the immunesystem, studied in peripheral blood over time.
Methods:
This is a non-randomised trial. Treatment by either surgery or SABR treatment for early stage (cT1-T2aN0M0) were determined by an institutional multi-disciplinary tumorboard, and in accordance with the patient’s preference . SABR was typically delivered in 3-8 fractions in 1-2 weeks, based on risk-adapted radiotherapy schemes that delivered a biologically effective dose of >100 Gy. Surgery generally involved a VATS lobectomy. Blood was collected prior to treatment, and at weeks 1, 2, 3 and 6 after start of treatment. The peripheral blood mononuclear cell (PBMC) fraction was isolated and was stimulated for 4 hours with phorbol 12-myristate 13-acetate (PMA) and ionomycin, to activate the T cells. Subsequently, the T-cells cells were harvested and analyzed by flow cytometry on the expression of CD4 and/or CD8, granzyme B and interferon (IFN) γ. As PD-1 expression is induced in T-cells after antigen exposure the expression of PD-1 was determined. Changes of population proportions between the different time points were analyzed with the related-samples Wilcoxon signed rank test.
Results:
23 early stage non-small cell lung cancer (NSCLC) patients were included in the study. Of these, 13 patients underwent surgical resection at a mean age (±standard deviation) of 62,9± 8,4 years, and 10 patients who underwent SABR at a median age of 70,0 ±10,4 years. SABR patients had more comorbidities, and a poorer WHO performance score, but clinical tumor stage was comparable. A significant increase in the proportion of IFNγ[+]Granzyme B[+] CD8 T cells (p<.05) was observed at week 2 in the SABR treated group, whereas no difference was found after surgical resection. The PD1[+] fraction of CD4[+] T cells was significantly increased at week 2 in the SABR treated group (p<.05), whereas no differences were seen at two weeks after surgical resection. Proportions of PD1[+ ]CD4 T cells remained elevated in the SABR group at week 3 and 6. A similar trend was observed in the CD8[+] T cell population, although this did not reach statistical significance (p<.1).
Conclusion:
SABR but not surgery, enhances T-cell activation and PD-1 upregulation. The results of our study warrant further investigation as to whether SABR induces an anti-tumor response in patients with early stage NSCLC . The upregulation of PD-1 inherently accompanied with this activation of the immune system potentially warrants combination treatment with PD-(L)1 blockade.
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MINI18.08 - A Systematic Review of Comparative Effectiveness Studies of Surgery versus SABR in Early Stage Lung Cancer: How Good Is the Data? (ID 1549)
17:25 - 17:30 | Author(s): S. Senan
- Abstract
- Presentation
Background:
Three prospective randomized control trials (RCTs) comparing stereotactic ablative radiotherapy (SABR) and surgery in early stage non-small cell lung cancer (ES-NSCLC) failed to complete accrual. Numerous other comparative effectiveness studies have been published, but such studies may be more prone to bias, and conclusions may vary based on study quality. The goal of this study was to perform a systematic review of comparative effectiveness studies that compare both treatment modalities in this patient population, to assess study quality and conclusions.
Methods:
In accordance with PRISMA guidelines, a systematic review was conducted on studies reporting on comparative outcomes of surgery versus SABR for ES-NSCLC. Studies published in the English language over a 10-year period (April 2006-March 2015) were identified using PUBMED with an inclusive search strategy, using the National Library of Medicine’s medical subject headings. Eligible study designs included RCTs, population analyses, match pair comparisons, propensity-match score comparisons, retrospective case-control series, decision analyses, and cost-effectiveness analyses. Letters, editorial and systematic reviews were excluded. Abstracts identified were independently reviewed by two investigators to determine eligibility, with discrepancies settled by a third investigator. Using a standardized data abstraction form, study, patient, tumor, and treatment characteristics were abstracted. As patients undergoing surgery and SABR often differ in their baseline characteristics, we determined the proportion of studies reporting statistical adjustment for baseline characteristic imbalances (e.g. matching in patient studies, sensitivity analyses in modeling studies). The Fisher’s exact test was used to determine if there was an association between the use of statistical adjustment and differences in overall survival (OS) findings.
Results:
Of the 568 studies identified by our search strategy, 22 were eligible for analysis. Primary study design was retrospective (n=11), population-based (n=7), or model-based (n=4). Most patient studies (n=17) reported on a statistical adjustment for differences in baseline characteristics, with propensity score matching (n=12) being the most common technique employed. All studies, except for 1, reported details of the type of surgery performed. SABR doses employed ranged from 30 Gy in 1 fraction, to 60 Gy in 3 fractions. The weighted average pathologic confirmation of malignancy rate for SABR patients was 72% (range 22-100%). Of the 20 studies reporting on overall survival, 12 found that SABR and surgery were equal, or sensitive to variability in baseline patient, treatment, or tumor factors. The remaining 8 studies reported an overall survival benefit of surgery over SABR, however, 4 of these studies did not employ statistical adjustments for baseline characteristics. In the other 4 studies reporting overall survival superiority of surgery when controlling for various co-variates, at least one other recurrence endpoint (local, regional, or distant) was found to be equal between surgery and SABR. All but 2 studies stated in their conclusion that future clinical trials are warranted to investigate the role of SABR in the potentially operable ES-NSCLC patient.
Conclusion:
A systematic review of the comparative effectiveness literature indicates that the results of well-controlled studies comparing surgery and SABR argue for clinical equipoise. Results of a pooled analysis of two international RCTs that closed prematurely are expected shortly.
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MINI 32 - Topics in Localized Lung Cancer (ID 166)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:D. Boffa, T. D'Amico
- Coordinates: 9/09/2015, 18:30 - 20:00, 201+203
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MINI32.14 - Primary Early-Stage Lung Cancer Following Head and Neck Cancer: A Population Based Study of Treatment and Survival in the Netherlands (ID 1433)
19:45 - 19:50 | Author(s): S. Senan
- Abstract
- Presentation
Background:
Second primary lung cancer (SPLC) is an important cause of death in survivors of head and neck squamous cell cancer (HNSCC). The goal of this Dutch population study was to compare treatment patterns and outcomes in early-stage SPLC after HNSCC.
Methods:
Details on all patients in a population of 16 million diagnosed with lung cancer between 1997 and 2011 were obtained from the Netherlands Cancer Registry. After excluding patients with a history of other malignancies, patients were dichotomized with a primary lung cancer or a SPLC after HNSCC. The latter included oral cavity, oropharynx, larynx, and hypopharynx sub-sites. Baseline characteristics of early-stage primary and SPLC were compared using the chi-square, fisher’s exact, or t-test, where appropriate. After stratifying patients into five consecutive 3-year time periods, the Chi-Square Trend test was used to determine trends in treatment patterns over time. Overall survival was calculated using the Kaplan-Meier method, and the log-rank test used to assess differences in survival. 30- and 90-day treatment related mortality were calculated. To assess for stage migration due to routine availability of PET-staging, as well as the availability of stereotactic ablative radiotherapy (SABR), outcomes were analyzed before and after 2005. All statistical tests were two-sided and considered significant when p<0.05.
Results:
Of the 153,330 lung cancer patients, 19,501 with a history of a non-HNSCC primary cancer were excluded from the analysis. Of the 133,829 remaining patients, 2,556 (2%) represented a SPLC following HNSCC. SPLC patients were more likely to present in stage I (27% versus 16%, p<0.01) rather than stage IV (34% versus 44%, p<0.01). For early-stage SPLC, initial HNSCC anatomical subsites were most commonly larynx (53%) and oral cavity (24%). Treatment for early-stage SPLC included surgery (53%), radiotherapy (RT, 33%), or best supportive care (14%). The proportion of RT patients undergoing SABR was unknown. When compared to surgery, early-stage SPLC patients receiving any-form of RT tended to be older, with more advanced T-stage disease, poorly differentiated histology, and lower rates of pathologic diagnosis (all p<0.01). The proportion of all early-stage lung cancer patients receiving surgery over time remained stable in the primary setting (range: 59-63%, p=0.69), but decreased for early-stage SPLC patients (range: 68-42%, p<0.01). The use of RT increased over time for both primary (range: 21-30%, p<0.01) and early-stage SPLC patients (range: 23-43%, p<0.01). 30- and 90-day treatment related mortality rates were higher in surgical versus RT patients in both pre-2005 (3.8%, 8.6% versus 4.0%, 8.0%) and post-2005 (2.3%, 4.0% versus and 0%, 3.2%) eras. Overall, early-stage SPLC surgical patients had improved survival when compared to RT patients (p<0.01). In the post 2005 era, however, survival was similar for these two modalities (p=0.13).
Conclusion:
In survivors of HNSCC who develop early-stage SPLC, RT deserves attention as an alternative gold standard to surgery. Previous studies indicated that a majority of RT delivered for early-stage NSCLC after 2006 was SABR [Palma D, 2010]. Despite negative selection of poorer baseline characteristics, use of RT resulted in comparable survival and lower post-treatment mortality when compared to surgery in the modern era.
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ORAL 10 - SCLC (ID 98)
- Event: WCLC 2015
- Type: Oral Session
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:C. Faivre-Finn, P. Lara Jr.
- Coordinates: 9/07/2015, 10:45 - 12:15, 605+607
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ORAL10.03 - Which Patients with ES-SCLC Should Receive Thoracic Radiotherapy (TRT) Routinely? (ID 41)
11:27 - 11:38 | Author(s): S. Senan
- Abstract
- Presentation
Background:
Although TRT in patients with ES-SCLC did not lead to a statistically significant difference in overall survival (p=0.066), it did improve 2-year survival rates (p=0.004) in the CREST trial (Slotman et al., Lancet 385:36-42:2015). The failure to meet the primary study endpoint has evoked some controversy in the lung cancer community as to which patients should be offered TRT routinely. To define which patients benefit most from radiotherapy, analysis for overall survival (OS), progression free survival (PFS) and recurrence pattern was performed in patients with and without RITD, which was one of the stratification factors in the randomized study.
Methods:
Patients with confirmed ES-SCLC who responded to 4-6 cycles of platinum-etoposide were randomized to TRT (30 Gy/10fx) or control. All received prophylactic cranial irradiation (PCI). The primary study endpoint was OS. Secondary endpoints were PFS, intrathoracic control. relapse pattern and toxicity.
Results:
Out of 495 patients in the intent-to-treat analysis, 434 had RITD (215 allocated to TRT and 219 to the control arm) and 61 had not (32 allocated to TRT and 29 to the control arm). No significant differences in patient characteristics were observed between the groups. In patients with RITD, OS was significantly longer in the TRT-arm (HR 0.81,95% CI 0.66-1.00;p=0.044). Survival rates in the TRT and control arm were 33% (95%CI 27-40) vs 26% (95%CI 21-33) at 1 year, and 12% (95%CI 8-19) vs. 3% (95%CI 1-8) at 2 years, respectively. PFS was also significantly longer in the TRT-arm (HR=0.70, 95%CI 0.57-0.85; p<0.001). Intrathoracic progression was reported in 43.7% of the TRT arm vs. 81.3% in the control arm (p<0.001). There was no significant difference in the risk of brain metastases (10.2% vs. 5.5%). Exclusive progression outside thorax and brain occurred in 37.2% in the TRT arm, compared to 5.9% in the control arm (P<0.001). In patients without RITD, there was no significant difference in OS (HR 1.02, 95%CI 0.59-1.77, p=0.937) and PFS (HR=1,00, 95%CI 0.59-1.70, NS) between the TRT and control arms.
Conclusion:
This additional analysis of the CREST data shows that ES-SCLC patients with RITD after chemotherapy have a statistically significant improvement in OS, PFS and risk of intrathoracic progression if they undergo TRT. No such benefit for TRT is seen in patients without RITD. These findings support the routine use of TRT in patients who respond to chemotherapy but still have residual intrathoracic disease.
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.02 - Safety Results of the Consolidation Phase of a Phase III (PROCLAIM): Pemetrexed, Cisplatin or Etoposide, Cisplatin plus Thoracic Radiation Therapy followed by Consolidation Cytotoxic Chemotherapy in Locally Advanced Nonsquamous Non-Small Cell Lung Cancer (ID 645)
10:56 - 11:07 | Author(s): S. Senan
- Abstract
- Presentation
Background:
Standard treatment for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy. However, many patients die from recurrent disease, indicating that new treatment strategies are needed.
Methods:
PROCLAIM is a phase III trial comparing overall survival in patients with unresectable stage III nonsquamous NSCLC receiving pemetrexed+cisplatin (PemCis) and concurrent radiotherapy for 3 cycles followed by 4 cycles of pemetrexed consolidation (Arm A) versus etoposide+cisplatin (EtoCis) and concurrent radiotherapy for 2 cycles followed by consolidation with a platinum-based doublet of choice for up to 2 cycles (Arm B). Possible consolidation therapies in Arm B were EtoCis, vinorelbine+cisplatin (VinCis), and paclitaxel+carboplatin (PacCarb). Overall efficacy and safety results for the intent-to-treat population will be presented in a separate disclosure. Safety was a secondary objective. Interim safety results for the concurrent phase were previously presented. Here we present safety results for the consolidation phase. Treatment-emergent adverse events (TEAEs) were assessed according to the Common Terminology Criteria for Adverse Events (v3.0, CTCAE). TEAE incidences were compared using Fisher’s exact test (two-sided α=0.05).
Results:
Of 598 randomized patients, 555 were treated in the concurrent phase (Arm A: N=283; Arm B: N=272), most of whom (Arm A: n=229 [80.9%]; Arm B: n=202 [74.3%]) continued on to the consolidation phase (Arm B patients: EtoCis [33.5%], PacCarb [26.8%], VinCis [14.0%]). Baseline characteristics, including age, gender, performance status, smoking status, stage, and origin, were well-balanced across arms. Percentages of patients in Arm A completing ≥2, ≥3, and 4 consolidation cycles were 95.2%, 84.3%, and 73.4%, respectively. Percentages of patients in Arm B completing 2 consolidation cycles (maximum) were EtoCis (89.0%), PacCarb (93.2%), and VinCis (86.8%). Mean dose intensities for pemetrexed, etoposide, vinorelbine, cisplatin, paclitaxel, and carboplatin were 95.4%, 94.0%, 84.2%, 91.2%, 88.7%, and 92.7%, respectively. More patients in Arm B, compared to Arm A, experienced dose reductions, dose omissions, and cycle delays. Patients in Arm B reported more grade 3/4/5 drug-related TEAEs than Arm A (51.0% versus 31.0%, p<0.001; Table). Rates of drug-related serious AEs were similar between groups (Arm A: 14.4%; Arm B: 13.4%).Drug-related Grade 3/4/5 TEAEs Occurring in ≥2% of Patients (or of Clinical Relevance) in the Consolidation Phase
CTCAE Arm A (N=229) n (%) Arm B (N=202) n (%) Neutrophils 27 (11.8) 76 (37.6)* Leukocytes 19 (8.3) 29 (14.4) Hemoglobin 6 (2.6) 9 (4.5) Platelets 5 (2.2) 10 (5.0) Febrile neutropenia 7 (3.1) 7 (3.5) Lymphopenia 8 (3.5) 5 (2.5) Pneumonitis/pulmonary infiltrates 5 (2.2) 2 (1.0) Fatigue 2 (0.9) 4 (2.0) Pneumonia 5 (2.2) 0 Esophagitis 0 3 (1.5) *p<0.001, Fisher’s exact test. Note: Of the TEAEs listed here, only one case (0.4%, Arm A, pneumonia) was grade 5.
Conclusion:
During the PROCLAIM consolidation phase, most patients were able to complete the planned number of cycles in either arm, with the highest dose intensity corresponding to pemetrexed. Pemetrexed consolidation had a significantly lower incidence of drug-related grade 3/4/5 TEAEs than the platinum doublets in Arm B. A more detailed analysis of Arm B (by treatment regimen) is underway.
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ORAL 35 - Surgical Approaches in Localized Lung Cancer (ID 155)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:M. de Perrot, J. Mitchell
- Coordinates: 9/09/2015, 16:45 - 18:15, 601+603
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ORAL35.03 - Salvage Surgery for Local Failures after Stereotactic Ablative Radiotherapy for Lung Malignancies (ID 626)
17:07 - 17:18 | Author(s): S. Senan
- Abstract
- Presentation
Background:
Stereotactic ablative radiotherapy (SABR) is a guideline-recommended therapy for unfit patients with early stage non-small cell lung cancer (NSCLC), and for pulmonary metastases. Experience with SABR for potentially operable patients is also increasing, and salvage surgery may have a role in patients who subsequently develop a local tumor recurrence. However, prior high-dose SABR could theoretically increase local adhesions and compromise wound healing. As the published literature is limited, we describe our experience with salvage surgery in 17 patients who developed a local recurrence after SABR.
Methods:
Patients who underwent surgical salvage for a local recurrence following SABR for pulmonary malignancies were identified from two Dutch institutional databases, as well as cases provided by other Dutch surgeons. Complications were scored using the Dindo-Clavien-classification.
Results:
Seventeen patients who underwent surgery for a local recurrence were identified. Patients were treated with SABR for either primary non-small cell lung cancers (N=9) or solitary metastasis (N=8). Four patients with solitary metastasis underwent surgery twice each for separate recurrences. Median time to local recurrence was 15.6 months. Recurrences were diagnosed with CT- and/or [18]FDG-PET-imaging, with 5 patients also having a pre-surgical pathological diagnosis. Extensive adhesions were observed during 5 resections, requiring conversion from a thoracoscopic procedure to thoracotomy in 3 procedures. Four patients experienced complications post-surgery; grade 2 (N=2) and grade 3a (N=2), respectively. All resected specimens confirmed the presence of viable tumor cells. Median length of hospital stay was 7 days (range 4-15 days) and 30-day mortality was 0%. Lymph node dissection revealed mediastinal metastases in 3 patients, all of whom received adjuvant therapy. Median follow-up after surgery was 41 months and median overall survival was 38 months.
Conclusion:
Experience with 21 surgical procedures for local recurrences post-SABR revealed only two grade IIIa complications, and a 30-day mortality of 0%. Median overall survival after surgery was 38 months. These results suggest that salvage surgery may be safely performed in selected patients following SABR.
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PC 01 - Pro vs Con: Surgery vs. SBRT in Operable NSCLC / Pro vs Con: SBRT for Non-Biopsied Lung Nodules (ID 47)
- Event: WCLC 2015
- Type: Pro Con
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:D. Harpole, P. Yang, P. Bonomi, A. Wozniak
- Coordinates: 9/07/2015, 14:15 - 15:45, 601+603
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PC01.01 - Surgery vs. SBRT in Operable NSCLC - SBRT (ID 2026)
14:20 - 14:40 | Author(s): S. Senan
- Abstract
- Presentation
Abstract:
Stereotactic ablative radiotherapy (SBRT, or SABR) is the guideline-recommended treatment for a peripheral stage I non-small cell lung cancer in patients who are unfit for surgery, or those who decline surgery. In patients fit to undergo surgery, no phase three randomized trial comparing the two modalities has been completed to date. However, comparative effectiveness research suggests that a similar disease-free survival and loco-regional control can be achieved with the two modalities [Louie AV 2015a]. At present, the only available prospective randomized data available in operable NSCLC reveals a 3 year rate of freedom from local recurrence of 96% (95% CI 89–100) in patients treated using SBRT, compared with 100% (95% CI 100–100) for patients in the surgery group (log-rank p=0.44) [Chang J, 2015]. With a number of new randomized clinical trials now in preparation, it is useful to understand the main reasons for a reluctance to believe that 2 treatment modalities are comparable. The poorer overall survival reported in the SBRT literature led to the suggestion that early deaths may be due to poor disease control and/or unrecognized toxicity. However, patients treated in early studies of SBRT often had multiple comorbidities, a factor which also decreases survival in surgical patients. For example, data from the Danish Cancer registry on resected patients reported a 5-year overall survival of 38% (95% confidence interval 23-53%) for pT1 and Charlson comorbidity score 3+, versus a 5-year overall survival of 69% (CI 62-75%) for pT1 and no comorbidity [Luchtenborg M, 2012]. An externally validated prognostic validation tool consisting of a recursive partitioning analysis (RPA) and nomogram, the Amsterdam prognostic model (APM), has been developed for overall survival after SBRT [Louie AV, 2015b]. While the nomogram retained strong performance across surgical and SBRT external validation datasets, RPA performance was poor in surgical patients, suggesting again that two distinct patient populations are now being treated with these local modalities. It has been argued that the identification of nodal metastases during surgery, followed by adjuvant chemotherapy, can lead to superior survival with surgery, as occult nodal metastases may be missed in patients who undergo SBRT after PET-CT staging. However, even recent surgical publications indicate that guideline-specified nodal staging is not being performed in a significant number of patients, but that this difference was not detrimental. Danish Cancer Registry data revealed that nodal upstaging for clinical stage I NSCLC was lower after VATS than after open lobectomy, but also that that the extent of nodal harvest did not influence overall survival [Licht PB, 2013]. The IELCAP investigators reported on outcomes in 347 patients, where of the patients undergoing sub-lobar resection and lobectomy, more than 40% and approximately one quarter, respectively, did not even have a single mediastinal lymph node biopsied [Altorki NK, 2014]. We previously argued that the benefits of surgical nodal harvest are modest at best in this patient population. The lack of clear benefit for a nodal dissection, particularly in patient groups with a stage I NSCLC at increased risk of postoperative complications will limit the benefits of primary surgery. This is not a totally unexpected finding as recent studies have shown that more extensive nodal surgery was not beneficial in malignancies of the breast, esophagus and stage III melanomas with micrometastasis to the sentinel nodes. Cost-effectiveness analyses have consistently demonstrated that SBRT is cost-effective when compared to sublobar resection [reviewed in Louie AV, 2015]. Survivors of both surgery and SBRT are at risk of a second primary lung cancer, at a rate varying from 3-6% per person year [Lou F, 2013; Verstegen N, in press]. Lung cancer deaths predominate in the first 5 years after treatment, after which the relative contribution of cardiovascular and COPD causes of death increases [Janssen-Heijnen M, 2015]. It has been argued previously that “to expose patients to a hypofractionated SABR without mature evidence of absence of its toxicity would be hazardous” [van Schil P, 2013]. As long-term follow-up data after SABR is now available [Verstegen N, 2015], and as SABR has clearly fewer post-treatment complications than a surgical resection [Chang J, 2015], it is only appropriate to discuss all these findings with patients in the context of shared decision-making. Much of the recent debate has focused on pathological staging and techniques. However, there is growing awareness of the importance of ‘value in healthcare’. Both patients and their insurers increasingly wish to know what their life will be like after treatment, if they will return to work, and if their symptoms will improve [http://www.ichom.org/]. In the near future, patient reported outcome measures (PROMs) are likely to take a complimentary role in decisions about the choice of local therapy for stage I NSCLC, as high-quality data from randomized clinical trials are awaited. References Louie AV. Management of early-stage non-small cell lung cancer using stereotactic ablative radiotherapy: Controversies, insights, and changing horizons. Radiotherapy and Oncology 2015 ;114:138-47. Chang JY. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol. 2015;16:630-7. Lüchtenborg M. The effect of comorbidity on stage-specific survival in resected non-small cell lung cancer patients. Eur J Cancer. 2012 48:3386-95 Louie AV. Predicting Overall Survival following Stereotactic Ablative Radiotherapy in Early-Stage Lung Cancer: The Amsterdam Prognostic Model. Int J Rad Oncol Biol Phys in press. Licht PB. A national study of nodal upstaging after thoracoscopic versus open lobectomy for clinical stage I lung cancer. Ann Thorac Surg. 2013;96:943-9; Altorki NK. Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules. J Thorac Cardiovasc Surg. 2014 Feb;147:754-62; Lou F. Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance. J Thorac Cardiovasc Surg. 2013 ;145:75-81 Verstegen NE. Patterns of disease recurrence after SABR for early stage non-small cell lung cancer: Optimizing follow-up schedules for salvage therapy. J Thorac Oncol in press Janssen-Heijnen ML. Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis. Ann Oncol. 2015;26:902-7 van Schil PE. Surgery or radiotherapy for early-stage lung cancer--a potential comparison bias. Lancet Oncol. 2013;14(10):e390.
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